Final Program and Proceedings - 5th International Regional "Stress and Behavior" Neuroscience and...

5th Regional Stress and Behavior ISBS Conference, June 22-24, 2015, Miami, FL, USA 1

International STRESS AND BEHAVIOR Society (ISBS) ZENEREI Institute, USA

Program and Proceedings

5th International Regional (North America) ISBS Neuroscience and Biological Psychiatry

Stress and Behavior Conference

Miami, FL, USA June 22-24, 2015


IN PARTNERSHIP WITH:


CONFERENCE PROGRAM

Day 1. Mon, June 22, 2015 Royal Ballroom, Courtyard Miami Downtown/Brickell Area, 200 SE Second Avenue, Miami, FL

09.00-17.00 REGISTRATION

Morning session

10.00-10.30 ISBS OPENING AND WELCOMING. INDUCTION OF ISBS FELOWS

10.30-11.30 ISBS OPENING PLENARY LECTURE: UNDERSTANDING PTSD FROM BIOLOGICAL, COGNITIVE AND EVOLUTIONARY PERSPECTIVES. DM Diamond, Departments of Psychology, Molecular Pharmacology and Physiology, University of South Florida, and Research and Development Service, J.A. Haley VA Hospital, Tampa, FL, USA

11.30-12.00 ISBS PRESIDENTIAL LECTURE: CROSS-DOMAIN PARSING OF GENETICS OF COMPLEX NEUROPSYCHIATRIC DISORDERS: FROM DOMAIN GENES TO ANGEL GENES? AV Kalueff, ISBS Fellow, Research Institute for Marine Drugs and Nutrients (RIMDN) and College of Food science and Technology, Guangdong Ocean University, Zhanjiang, China; ZENEREI Institute, New Orleans, USA; Institute for Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia

12.00-12.40 ISBS SPECIAL FOCUS TALK: NORIBOGAINE MULTITARGET-DIRECTED PHARMACOLOGY: A CANONICAL RECIPE FOR ADDICTION AND ANXIETY RELATED DISORDERS? EL Maillet, DemeRx Inc., R&D Laboratory, Miami, FL, USA

12.40-13.50 LUNCH BREAK (FREE TIME) AND EXHIBITION

Afternoon session

13.50-17.40 ZUKOWSKA SYMPOSIUM ON STRESS NEUROSCIENCE Chairs: D Diamond (USA), S Nakamura, ISBS Fellow (Japan)

13.50-14.00 INTRODUCTION: PROFESSOR ZOFIA M ZUKOWSKA

14.00-14.15 BEHAVIORAL INHIBITION AND UNCERTAINTY ENHANCE CLASSICAL EYEBLINK CONDITIONING: SUPPORT FOR A LEARNING DIATHESIS MODEL OF ANXIETY DISORDERS. MT Allen, CE Myers, RJ Servatius, University of Northern Colorado, Greeley, CO, Stress and Motivated Behavior Institute, Newark, NJ, Department of Veterans Affairs, NJ Healthcare System, East Orange, NJ, NJ Medical School, Rutgers University, Newark, NJ, USA

14.15-14.30 NEUROTROPHIC FACTOR-1 PREVENTS STRESS-INDUCED DEPRESSION THROUGH FGF2 MEDIATED NEUROGENESIS. Y Cheng, Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver


National Institute of Child Health and Human Development (NICHHD), NIH, Bethesda, MD, USA

14.30-14.45 HEART RATE VARIABILITY ENHANCED DURING MINDFULNESS MEDITATION FOLLOWING STRESS-INDUCTION: A STRATIFIED-RANDOMIZED TRIAL WITH MALADAPTIVE PERFECTIONISTS. M Abid Azam, York University, Toronto, Ontario, Canada

14.45-15.00 PHARMACOLOGICAL STRESSOR ENHANCES MOTIVATION FOR FOOD REWARD IN SATIATED RATS: IMPLICATIONS FOR OVEREATING AND OBESITY. X Liu, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA

15.00-15.15 META-ANALYSIS OF THE EFFICACY AND SAFETY OF PRAZOSIN VERSUS PLACEBO FOR THE TREATMENT OF NIGHTMARES AND SLEEP DISTURBANCES IN ADULTS WITH POST-TRAUMATIC STRESS SYMPTOMS. L Ruth, K George, L Kebejian, S Himelhoch, Department Of Psychiatry, University of Maryland Medical School, Baltimore, MD, USA

15.15-15.30 A PIVOTAL ROLE OF OREXIN (HYPOCRETIN) NEURONS IN STRESS-INDUCED THERMOGENESIS. T Kuwaki, Department of Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

15.30-16.00 COFFEE BREAK AND EXHIBITION

16.00-16.35 THE IMPACT OF FLOTATION RESTRICTED ENVIRONMENTAL STIMULATION THERAPY (REST) ON HEART RATE, CORTISOL, AND PERCEIVED STRESS LEVELS. G Talley, A Jahromi, Float On LLC and Float Conference, Portland, OR, USA

16.35-16.50 EFFECT OF STRESS ASSOCIATED NEUROTRANSMITTERS ON THE MEDIODORSAL PREFRONTAL CORTEX. B Nagy, I Szab, B Csetnyi, E Hormay, Z Kardi, University of Pcs, Medical School, Institute of Physiology, Pcs, Hungary

16.50-17.10 EFFECTS OF AIR TRAVEL STRESS ON THE CANINE MICROBIOME A PILOT STUDY. EB Venable, SD Bland, HD Holscher, KS Swanson, Department of Animal Science Food and Nutrition, Southern Illinois University, Department of Animal Sciences, University of Illinois at Urbana-Champaign, IL, USA

17.10-17.40 PRESENTATION: BIOSEB EB INSTRUMENTS: MJ Craddock, Bioseb In Vivo Research Instruments, Pinellas Park, FL, USA

Social Program: 7pm Miami Boat Tour (admissions)


Day 2. Tue, June 23, 2015 Royal Ballroom, Courtyard Miami Downtown/Brickell Area, 200 SE Second Avenue, Miami, FL


Morning session

10.00-10.30 ISBS LECTURE: NEUROPSYCHOLOGICAL DEVELOPMENT IN INTERACTION BETWEEN PHYSICAL AND BIOLOGICAL ENERGY. M Koshiba, ISBS Fellow, G Karino, K Mimura, H Tokuno, S Usui, I Tanaka, Y Honda, T Kodama, K Sato, H Kishino, M Shukuya, T Kunikata, S Nakamura, ISBS Fellow, H Yamanouchi, Saitama Medical University, Saitama, Tokyo University of Agriculture and Technology, TMIM, NCNP, University of Tokyo, Tokyo City University, Tokyo, Japan

10.30-12.30 LAPIN SYMPOSIUM ON BIOLOGICAL PSYCHIATRY Chairs: M Koshiba, ISBS Fellow (Japan), AV Kalueff, ISBS Fellow (USA)

10.30-10.40 INTRODUCTION: PROFESSOR IZYASLAV (SLAVA) P LAPIN

10.40-10.55 THE EFFECT OF DEXMEDETOMIDINE ON MORPHINE-INDUCED DEPENDENCE IN RATS. TB Uskur, MA Barlas, AG Akkan, Istanbul University, Faculty of Medicine Cerrahpasa, Medical Pharmacology, Istanbul, Turkey

10.55-11.10 SELF-OBSERVATION, REFLECTION AND COPING WITH BRAIN CHEMISTRY IN ADOLESCENT COMPETING TENNIS PLAYERS. PW Wightman, H Anselmi, Argentina National Training Center Elite Athletes, University L Zamora, Lomas Zamora, Argentina


11.35-12.00 ASSESSING GENDER DIFFERENCE IN AGGRESSION AMONG AUTISTIC CHILDRENS PARENTS. R Mittal, Civil Hospital, Moga, Punjab, India

12.00-12.15 TELOMERASE DYSREGULATION IN THE HIPPOCAMPUS OF A RAT MODEL OF DEPRESSION. NORMALIZATION BY LITHIUM. Y Wei, L Backlund, G Wegener, A Mathe, C Lavebratt, Neurogenetics Unit, Center for Molecular Medicine (CMM), Karolinska University Hospital, Stockholm, Sweden

12.15-12.30 PROTEIN BASED DIAGNOSTIC BIOMARKERS FOR EARLY DIAGNOSIS OF ALZHEIMERS DISEASE. DP Katare, RJ Mani, Center of Medical Biotechnology, Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India

12.30-14.00 LUNCH BREAK (FREE TIME) AND EXHIBITION


Afternoon session

14.00-18.00 INTERACTIVE POSTER SESSION

DO SINGLE EXPERIENCES OF CHILDHOOD ABUSE INCREASE DEPRESSION AND ANXIETY SYMPTOMS IN ADULTHOOD? W Rehan, A Johansson, P Santtila, Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland

COMPARING PSYCHOLOGICAL MORBIDITY AMONG STUDENTS APPEARING FOR FINAL PROFESSIONAL MBBS EXAMINATION AND CIVIL SERVICES EXAMINATION. A Sharma, M Singla, BS Sidhu, Department of Psychiatry, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India

IMPACT OF CHILDHOOD ADVERSITY AND VASOPRESSIN RECEPTOR 1A VARIATION ON SOCIAL INTERACTION IN ADULTHOOD: A CROSS-SECTIONAL STUDY. J Liu, C Lavebratt, Y Forsell, School of Nursing, Shandong University, Jinan, China; Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

EFFECTS OF MOBILE TECHNOLOGY USE ON MOOD AND BODY MASS INDEX. CB Shay, C Hansen, Keiser University, Ft. Lauderdale, FL, USA

AMYGDALA INVOLVEMENT IN AVOIDANCE ACQUISITION IN A BEHAVIORALLY INHIBITED RAT STRAIN. DP Miller, KM Moench, KCH Pang, RJ Servatius, Carthage College, Kenosha, WI, Stress and Motivated Behavior Institute, Newark, NJ, Department of Veterans Affairs, NJ Healthcare System, East Orange, NJ, NJ Medical School, Rutgers University, Newark, NJ, USA

EEG BIOFEEDBACK AND LAVENDER AROMATHERAPY IN MIGRAINE - A PRELIMINARY STUDY. HH Bauer, SM Nagel, College of Human Medicine, Michigan State University, East Lansing, MI; Department of Psychology, Saginaw Valley State University, University Center, MI, USA

EARLY LIFE STRESS AND THE BRAIN-GUT-MICROBIOTA AXIS: IMPACT OF N-3

POLYUNSATURATED FATTY ACIDS. MM Pusceddu, S El Aidy, P Kelly, JF Cryan, TG Dinan, Department of Psychiatry, Alimentary Pharmabiotic Centre, Moorepark Food Research Centre, Teagasc, Fermoy Co., Department of Anatomy and Neuroscience; University College Cork, Cork, Ireland

THE USE OF MODERN TECHNOLOGY DURING TRAINING OF COGNITIVE PROCESSES. M Zubanska, A Bonus-Dziego, AK Zubrzycka, Police Academy in Szczytno, Szczytno, Poland

ENRICHED ENVIRONMENT DECREASED ANXIETY-RELATED BEHAVIOR IN AN ANIMAL MODEL OF GENERALIZED ANXIETY DISORDER. GP Dias, ACD Silveira, MCN Bevilaqua, AA Marques, G Cocks, J Landeira-Fernandez, S Thuret, AE Nardi, Universidade Federal do Rio de Janeiro UFRJ; Pontifcia Universidade Catlica, Rio de Janeiro, Brazil; Kings College London, London, UK

INCREASED RISK OF SEXUALLY TRANSMITTED DISEASES AFTER BEREAVEMENT A SWEDISH NATIONAL COHORT. E Bond, D Lu, E Herweijer, K Sundstrom, U Valdimarsdottir, K Fall, LA Dahlstrom, P Sparn, F Fang, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden


THE CYSTIN/GLUTAMATE ANTIPORTER AS A POTENTIAL NOVEL TARGET TO MODULATE THE STRESS RESPONSE? T Demuyser, E Bentea, L Deneyer, G Albertini, J Van Liefferinge, E Merckx, A Massie, I Smolders, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium

SEEKING SAFETY: A RANDOMIZED CLINICAL TRIAL. C Hansen, D Hien, Keiser University, Ft. Lauderdale, FL, Columbia University, City College of New York, NY, USA

DEVELOPMENT AND IN VITRO CHARACTERIZATION OF NEUROMEDIN U ANALOGS. A De Prins, C Betti, B Sivertsen, V Caveliers, A Van Eeckhaut, B Holst, S Ballet, I Smolders, Department of Pharmaceutical Chemistry and Drug Analysis, Department of Organic Chemistry, Department of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium; Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark

PSYCHOLOGICAL STRESS IN EARLY LIFE AFFECTS ADULT RATS IN A SEX-DEPENDENT MANNER. SR Melo, CTD Antoniazzi, S Hossain, B Kolb, State University of Maringa, Parana, Brazil

EVENT-RELATED POTENTIALS FROM PATIENTS WITH MAJOR DEPRESSIVE DISORDER WITH MELANCHOLIC FEATURES AND ANXIOUS DISTRESS. MV Pronina, GY Poliakova, YI Poliakov, VA Ponomarev, A Mller, JD Kropotov, NP Bechtereva Institute of the Human Brain RAS, Saint-Petersburg, Russia


THE IMPACT OF MATERNAL TRAUMA HISTORY ON PEDIATRIC ASTHMA CONTROL. M Corneille, I Barreiro, S Behbahani, Albizu University, Doral, FL, USA

PHARMACOGENETIC TESTING SHOWS UTILITY FOR PSYCHIATRIC PATIENTS. H Harris, R Scott, K Gardner, J Lombard, FX Brennan, Genomind Inc., Chalfont, PA, USA

CRY OVER THE PAST OR STRESS ABOUT THE FUTURE? TIME PERSPECTIVES PREDICT PAIN PERCEPTION AND CATASTROPHIZATION. B Gacs, A Csatho, University of Pecs, Medical School, Department of Behavioral Sciences, Pecs, Hungary

SIMULTANEOUS EXPOSURE TO CHRONIC MILD STRESS AND ENRICHED DIETS ENHANCE SPATIAL MEMORY VIA DIFFERENTIAL EXPRESSIONS OF DOPAMINE-4 AND METABOTROPIC GLUTAMATE-5 RECEPTORS. PD Shallie, OF Shallie, AK Adefule, Department of Anatomy, Olabisi Onabanjo University, Ago-Iwoye, Nigeria

EXAMINING THE RELATIONSHIP BETWEEN JOB STRESS, JOB SAFETY, AND JOB SATISFACTION. SM Guy, Keiser University, Ft. Lauderdale, FL, USA

IMPLICATIONS OF HEALTH CARE COSTS ON CARDIOVASCULAR DISEASE PATIENTS: A PSYCHONEUROIMMUNOLOGY PERSPECTIVE. I Barreiro, M Corneille, S Behbahani, ClinPharm, Albizu Universitry, Doral, FL, USA

EXAMINING THE ROLE OF COMMUNICATION AND SOCIAL SUPPORT AS A MEDIATOR OF STRESS RESILIENCE AMONG CLINICAL PSYCHOLOGY DOCTORAL STUDENTS. JC


Lyons, SR Webster, CA Feldman, B Nierenberg, Center for Psychological Studies, Nova Southeastern University, Ft. Lauderdale, USA

PERCEIVED DISCRIMINATION, ACCULTURATIVE STRESS, AND DEPRESSIVE SYMPTOMS IN MEXICAN AMERICANS: FAMILISM AND ETHNIC IDENTITY AS MODERATORS. H-L Cheng, JL Rislin, X Nguyen, C Williams, CH Cha, B Stamper, R Zamora, GA Liu, J Peters, New Mexico State University, Las Cruces, NM, USA

ULTRASONIC VOCALIZATION DURING EXPLORATION IN BOTH SAFE AND STRESSFUL ENVIRONMENT IN ADULT MALE MICE. H-S Mun, JC Roder, T Lipina, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

EXAMINING BEHAVIORAL DIFFERENCES BETWEEN WILD-CAUGHT AND DOMESTICATED (LABORATORY) ZEBRAFISH, DANIO RERIO. AV Kalueff, ISBS Fellow, S Homechaudhuri, C Song, S Li, Y Liu, A Mitra, S Pal, A Chaudhuri, A Roy, M Biswas, D Roy, A Podder, A Kaluyeva, P Chen, L Yang, JJ Wang, AM Stewart, ISBS Fellow, Research Institute for Marine Drugs and Nutrients, College for Food Science and Technology, Guangdong Ocean University, Zhanjiang, China; Department of Zoology, University of Calcutta, Kolkata, India; ZENEREI Institute and the International Zebrafish Neuroscience Research Consortium (ZNRC), New Orleans, USA; Institute for Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia

Social Program:

7pm Conference Dinner (admissions)


Day 3. Wed, June 24, 2015 Royal Ballroom, Courtyard Miami Downtown/Brickell Area, 200 SE Second Avenue, Miami, FL


Morning session

10.00-15.00 9th INTERNATIONAL ZEBRAFISH NEUROSCIENCE SYMPOSIUM AND WORKSHOP Chairs: AV Kalueff, ISBS Fellow (USA), DJ Echevarria, ISBS Fellow (USA)

10.00-10.10 INTRODUCTION: THE INTERNATIONAL ZEBRAFISH NEUROSCIENCE RESEARCH CONSORTIUM (ZNRC)

10.10-11.00 ZNRC LECTURE: ZEBRAFISH BIOLOGICAL PSYCHIATRY. DJ Echevarria, ISBS Fellow, Department of Psychology, University of Southern Mississippi, Hattiesburg, MS, USA

11.00-11.45 ZNRC PRESENTATION: FROM A TO Z: ACTIVITY ANALYSIS AND DETAILED OBSERVATIONS IN ZEBRAFISH. J Rogers, Noldus Information Technology Inc., Leesburg, VA, USA

11.45-12.15 ZNRC LECTURE: MODELING ACUTE AND CHRONIC STRESS IN ADULT ZEBRAFISH AN UPDATE. AV Kalueff, ISBS Fellow, S Li, Y Liu, P Chen, L Yang, JJ Wang, A Kaluyeva, AM Stewart, ISBS Fellow, C Song, Research Institute for Marine Drugs and Nutrients (RIMDN) and College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China; ZENEREI Institute and the International Zebrafish Neuroscience Research Consortium (ZNRC), New Orleans, USA; Dalhousie University, Halifax, Canada; Institute for Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia


Afternoon session

12.45-13.15 ZNRC PRESENTATION: VIEWPOINT. P-A Fel, ViewPoint, Montreal, Canada

13.15-13.30 ASSESSING THE EFFECTS OF LIGHT DARK MANIPULATION AND CAFFEINE EXPOSURE ON ZEBRAFISH SLEEP BEHAVIOR. KM Khan, DJ Echevarria, ISBS Fellow, NR Lodinger, AD Collier, Department of Psychology, University of Southern Mississippi, Hattiesburg, MS, USA

13.30-13.50 DISC1 MODULATES THE STRESS RESPONSE IN LARVAL ZEBRAFISH VIA HYPOTHALAMIC GENES. HL Eachus, J Wood, M Placzek, PJ Watt, Department of Animal and Plant Science, Bateson Centre, Department of Biomedical Science, Sheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, UK


13.50-14.05 THE EFFECTS OF METHYLENE BLUE ON LEARNING ACQUISITION IN THE ZEBRAFISH. EM Caramillo, DJ Echevarria, ISBS Fellow, Department of Psychology, University of Southern Mississippi, Hattiesburg, MS, USA

14.05-14.25 ADULT ZEBRAFISH AND CONDITIONED PLACE PREFERENCE AS A MODEL OF DRUG REWARD. AD Collier, NR Lodinger, KM Khan, EM Caramillo, DJ Echevarria, ISBS Fellow, Department of Psychology, University of Southern Mississippi, Hattiesburg, MS, USA

14.25-15.00 ROUND TABLE AND ASK-THE-EXPERT SESSION: FUTURE OF ZEBRAFISH MODELS IN TRANSLATIONAL NEUROSCIENCE RESEARCH

15.00-15.20 CLOSING CEREMONY ANNOUNCING FORTHCOMING ISBS CONFERENCES


CONFERENCE ABSTRACTS


Day 1. Mon, June 22, 2015 Royal Ballroom, Courtyard Miami Downtown/Brickell Area, 200 SE Second Avenue, Miami, FL

Morning session

ISBS OPENING PLENARY LECTURE: UNDERSTANDING PTSD FROM BIOLOGICAL, COGNITIVE AND EVOLUTIONARY PERSPECTIVES.

DM Diamond, Departments of Psychology, Molecular Pharmacology and Physiology, University of South Florida, and Research and Development Service, J.A. Haley VA Hospital, Tampa, FL, USA

Post-traumatic stress disorder (PTSD) is routinely described as a pathological or dysfunctional state because the persistent post-trauma symptoms, such as hyper-vigilance, increased startle response, intrusive memories, impaired sleep quality and a predisposition toward substance abuse cause traumatized people to suffer a reduced quality of life. In this presentation I will address the more global issue of whether the brain should be considered to be acting in a dysfunctional manner in a traumatized person that has developed PTSD. I will propose that there is heuristic value in considering that in the subset of traumatized people that develops PTSD, the brain is so protective of the individuals survival that it acts in a hyper-functional, rather than a dysfunctional, manner. More generally, I will suggest that PTSD symptoms reflect a hyper-protective status of the immune, cardiovascular, cognitive and neurobiological components of the stress response, which are influenced by ones genetic predisposition to maximize survival in response to a life-threatening attack. Therefore, all aspects of the stress response, and even the PTSD state, are adaptive from an evolutionary perspective, but are maladaptive in modern society because the unbridled and incessant preparation for a future attack takes its toll on ones physical and mental health.

ISBS PRESIDENTIAL LECTURE: CROSS-DOMAIN PARSING OF GENETICS OF COMPLEX NEUROPSYCHIATRIC DISORDERS: FROM DOMAIN GENES TO ANGEL GENES? AV Kalueff, ISBS Fellow, Research Institute for Marine Drugs and Nutrients (RIMDN) and College of Food science and Technology, Guangdong Ocean University, Zhanjiang, China; ZENEREI Institute, New Orleans, USA; Institute for Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia

Contemporary biological psychiatry uses both clinical and pre-clinical (animal) models to improve our understanding of brain pathogenesis. Modeling human psychiatric disorders is currently performed by targeting various key neurobehavioral clusters (domains) of phenotypic traits, such affective, cognitive, social, motor and reward. Analyses of such domains and their 'smaller units' (individual endophenotypes) are critical for the study of complex brain disorders and their neural underpinnings. The spectrum nature of brain disorders and the importance of pathogenetic linkage among various disordered domains or endophenotypes have also been recognized as an important strategic direction of translational research (Kalueff et al., 2015). I will critically discuss cross-domain analyses of animal models, and focus on their utility for mimicking the clinical overlap between disordered neurobehavioral domains in humans, and their potential role in discovering common (shared), unique (domain-specific) and novel putative interlinking (domain interplay) genes. In addition to novel putative class of bad pathogenic domain interplay genes, I will also propose the existence of protective angel interplay genes, which may exert protective effects either by 1) improving the cross-talk between genetic mechanisms of resistance or by 2) inhibiting the pathogenic function of putative disease-enhancing interplay genes.

ISBS SPECIAL FOCUS TALK: NORIBOGAINE MULTITARGET-DIRECTED PHARMACOLOGY: A CANONICAL RECIPE FOR ADDICTION AND ANXIETY RELATED DISORDERS? EL Maillet, DemeRx Inc., R&D Laboratory, Miami, FL, USA

Noribogaine is the stable and long-lived metabolite of ibogaine, the principal active of the herbal hallucinogen Iboga (ibogaine), which has demonstrated lasting beneficial effects in the domain of substance abuse in humans. Therapeutic potential of noribogaine itself was confirmed in pre-clinical studies where it attenuated the reinforcing properties of multiple substances of abuse including morphine, nicotine, cocaine and alcohol in rodents. It was also shown to reduce the pursuit or administration of nondrug reinforcers and


restore sensitivity to morphine in tolerant rodents. The mechanism of action was not defined but data suggested a canonical activity reminiscent of a multiplex modulation of the systems governing reward and disappointment. Noribogaine is, in fact, a polypharmacological drug which targets multiple neurotransmitter systems. Molecular characterization of its activity at its principal central targets was recently performed. Noribogaine displayed physiologically relevant potencies at inhibiting the 3-containing and 7 nAChR function, non-competitively inhibiting serotonin reuptake as well as displaying a profound biased agonism at the kappa opioid receptors which may correlate to a specific functional inhibition of CRF-mediated dynorphin/kappa dysphoric pathways in vivo. Thus, noribogaine appeared remarkably well-fit to target the emotional, motivational, and stress-related components of addiction. This pharmacological profile also constituted a basis for drug repurposing in the domain of mood and anxiety related disorders. Recent studies showed a direct activity of noribogaine at precluding novelty stress, a.k.a. anxiety in the novel tank, in zebrafish. The non-sedative anxiolytic action of noribogaine was also confirmed in the context of repeated nicotine withdrawal in zebrafish, confirming the therapeutic potential of noribogaine for challenging co-morbid states composite of addictive, mood and anxiety disorder spectra. RESEARCH SUPPORT: DemeRx, Inc.

Afternoon session

ZUKOWSKA SYMPOSIUM ON STRESS NEUROSCIENCE Chairs: D Diamond (USA), S Nakamura, ISBS Fellow (Japan)

INTRODUCTION: PROFESSOR ZOFIA M ZUKOWSKA.

This regular ISBS symposium is dedicated to Professor Zofia Zukowska (1949-2012). Professor Zukowska received her M.D. and Ph.D., trained in cardiovascular medicine at the Warsaw Medical Academy (Poland). She pursued post-doctoral training at the NIH, working with such renowned scientists as Irwin I. Kopin, Scientific Director of NINDS, and Julie Axelrod, Nobel Laureate. It was during this research period when her interest in stress and neuropeptides became galvanized. For the last 25 years, she was a professor (and, later, Chair) of the Department of Physiology and Biophysics at Georgetown University, before moving to the University of Minnesota as a new Stress Physiology Center Director. She assessed how stress affects cardiovascular and metabolic health and diseases, and the role of peptides, in particular neuropeptide Y (NPY), a sympathetic neurotransmitter and a stress mediator. She was the first to determine that

NPY mediates stress-induced prolonged vasoconstriction and vascular mitogenic and pro-atherosclerotic effects (via Y1 receptors) and potent angiogenic actions (via Y2 receptors), establishing the role of NPY in ischemia, retinopathy, tumors and obesity. Professor Zukowska was a strong supporter of ISBS and our conferences. Her scientific vision, extraordinary creativity, kindness to colleagues, and the talent to be daring, continue to inspire her ISBS colleagues and their research.

BEHAVIORAL INHIBITION AND UNCERTAINTY ENHANCE CLASSICAL EYEBLINK CONDITIONING: SUPPORT FOR A LEARNING DIATHESIS MODEL OF ANXIETY DISORDERS. MT Allen, CE Myers, RJ Servatius, University of Northern Colorado, Greeley, CO, Stress and Motivated Behavior Institute, Newark, NJ, Department of Veterans Affairs, NJ Healthcare System, East Orange, NJ, NJ Medical School, Rutgers University, Newark, NJ, USA

INTRODUCTION: Personality factors, such as behavioral inhibition, have been found to enhance associative learning in classical eyeblink conditioning and may be a diathesis for anxiety disorders. We recently reported that enhanced acquisition of conditioned eyeblinks in individuals self-reporting behavioral inhibition was more evident in an omission / yoked protocol in which the US was omitted on a CR trials (Holloway et al., 2014) and in partial reinforcement protocols with 50% paired trials (Allen et al., 2014) than in standard 100% CS-US paired training. In both omission/yoked protocols and partial reinforcement protocols, there is some degree of uncertainty as to when the next air puff will occur. The exclusion of the air puff on some trials also extends the inter-trial interval (ITI) between tone-air puff training trials. Therefore,


uncertainty and/or trial spacing effects may underlie our previous findings of enhanced associative learning in behaviorally inhibited individuals. In the current study, we tested the hypotheses that spacing trials by extending the ITI from 30 s to 57 s and by varying the ITI between 25 and 123 s would facilitate learning. METHODS: Eighty nine participants completed personality inventories (e.g., the Adult Measure of Behavioral Inhibition). Participants were grouped as behaviorally inhibited (i.e., anxiety vulnerable) and non-inhibited based on a median split of the AMBI scores. Delay eyeblink training consisted of 30 paired CS-US trials (500 ms/1200 Hz pure tone CS overlapping and co-terminating with a 50 ms, 5 psi corneal air puff US). Eyeblink responses were measured via silver chloride EMG electrodes. RESULTS AND DISCUSSION: Anxiety vulnerable individuals exhibited facilitated acquisition as compared to non-vulnerable individuals. Behaviorally inhibited individuals exhibited facilitated learning to the spaced trials with a variable ITI ranging from 25 to 123 s, but not with the 30 s or fixed 57 s ITI. Overall, enhanced sensitivity to forming stimulus associations in anxiety vulnerable individuals is most evident when the predictive relationship between the CS and US is uncertain. RESEARCH SUPPORT: This research was supported by the Stress and Motivated Behavior Institute and UNC.

NEUROTROPHIC FACTOR-1 PREVENTS STRESS-INDUCED DEPRESSION THROUGH FGF2 MEDIATED NEUROGENESIS. Y Cheng, Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHHD), NIH, Bethesda, MD, USA

Major depressive disorder is linked to stress. Prolonged, but not short-term, stress in mice leads to depressive-like behavior, indicating the existence of an allostatic mechanism. Here, we elucidated such a mechanism showing that hippocampal carboxypeptidase E, a new neurotrophic factor also known as NF-1, is up-regulated during short-term chronic restraint stress (CRS) in mice (which did not show depressive like behavior), resulting in enhanced fibroblast growth factor 2 (FGF2) expression and promotion of neurogenesis in the dentate gyrus, known to alleviate depressive-like behavior. In vitro study showed that NF-1directly up-regulated FGF2 expression through ERK-Sp1 signaling in primary cultured hippocampal neurons. Interestingly, Prolonged CRS in mice led to depressive-like behavior as well as decreased expression of NF-1 and FGF2. Genetic deletion of NF-1 in mice led to decreased hippocampal FGF2 and neurogenesis, and depressive-like behavior. Furthermore, exogenous FGF2 rescued the deficit in neurogenesis and depressive like behavior in NF-1 knock-out mice. These data identify CPE as a key modifier during short-term CRS to establish allostasis and prevent depressive-like behavior onset through enhancement of hippocampal FGF2 expression and neurogenesis. To evaluate the therapeutic potential for this pathway, we show that the drug rosiglitazone (Rosi), which has been reported to have anti-depressive activity in mice and humans, up-regulated endogenous NF-1 and FGF2 expression, in a NF-1dependent manner in hippocampal neurons. Furthermore, Rosi-treated mice showed increased NF-1 level and neurogenesis in hippocampus, indicating the antidepressant action of this drug. Therefore, NF-1-FGF2 pathway is a novel drug target for treatment of depression. RESEARCH SUPPORT: This research was supported by the NIH/NICHHD Intramural Program.

HEART RATE VARIABILITY ENHANCED DURING MINDFULNESS MEDITATION FOLLOWING STRESS-INDUCTION: A STRATIFIED-RANDOMIZED TRIAL WITH MALADAPTIVE PERFECTIONISTS. M Abid Azam, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada

INTRODUCTION: Heart rate variability (HRV) is a biomarker of cardiovascular function used to investigate chronic illness, psychopathology, cognitive stress and, more recently, attention and meditation. This study investigated HRV in relation to both maladaptive perfectionism (MP), a personality factor associated with cognitive stress, and mindfulness meditation (MM) - an attention regulation practice expected to promote cardiovascular recovery signified by increased HRV. METHODS: In a stratified-randomized trial, perfectionists (n = 21) and controls (n = 39) underwent a lab-based assessment obtaining HRV measures using electrocardiogram equipment. Data was obtained during a resting phase, a stress-induction phase, and a post-stress phase which involved randomization to a MM condition or a similar resting condition. RESULTS AND DISCUSSION: Statistical analyses revealed greater HRV was exhibited in post-stress MM compared to post-stress rest. There were significant within-subject increases in HRV of controls randomized to MM after stress-induction. These results support the effectiveness of MM in promoting cardiovascular recovery following cognitive stress. Further analyses revealed this effect was only present in


controls and not perfectionists. Psychophysiological models explaining how perfectionistic stress can impair cardiovascular recovery are discussed. Overall, more research is needed to elucidate the mechanisms of perfectionism and stress reduction through mindfulness to support the psychological and physiological health of clinical and subclinical populations.

PHARMACOLOGICAL STRESSOR ENHANCES MOTIVATION FOR FOOD REWARD IN SATIATED RATS: IMPLICATIONS FOR OVEREATING AND OBESITY. X Liu, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA

INTRODUCTION: Overeating beyond individuals homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods, especially with high calories (e.g., containing high-fat contents), are not fully understood. Exposure to stressful life events is proposed to be an environmental and psychological factors that are present in our ever-changing societies Here, we examined whether stress enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor receptor (CRF1) antagonism on the stress-enhanced motivation for food reward were also assessed. METHODS: Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive-ratio schedule for deliveries of either standard chow or high-fat food pellets. In the test sessions, rats received an intraperitoneal administration of yohimbine. In the rats trained with high-fat food pellets, the CRF1 receptor antagonist NBI was administered 20 min prior to yohimbine challenge. RESULTS AND DISCUSSION: The rats emitted higher levels of lever responses to procure the high-fat food reward compared with their counterparts on standard chow pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard pellets. Pretreatment with NBI effectively attenuated the enhancing effect of yohimbine challenge. Stress challenge significantly enhanced the motivation to procure food reward, especially the high-fat food. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our understanding of the biobehavioral mechanisms of overeating and obesity. RESEARCH SUPPORT: This work was supported by NIH Grants R01DA017288 and R01DA037277 from NIDA.

META-ANALYSIS OF THE EFFICACY AND SAFETY OF PRAZOSIN VERSUS PLACEBO FOR THE TREATMENT OF NIGHTMARES AND SLEEP DISTURBANCES IN ADULTS WITH POST-TRAUMATIC STRESS SYMPTOMS. L Ruth, K George, L Kebejian, S Himelhoch, Department of Psychiatry, University of Maryland Medical School, Baltimore, MD, USA

BACKGROUND: Sleep disturbances can have profound deleterious effects on the well-being of adults with post-traumatic stress symptoms (PTSS), even after adequate trials with antidepressants (Green et al., 2014). Prazosin can mitigate sleep disturbances and improve overall functioning, yet its use is not widespread. The aim of this meta-analysis is to assess the efficacy and safety of prazosin versus placebo for the reduction of nightmares, sleep disturbances, and illness severity in adults with post-traumatic stress symptoms (PTSS). METHODS: Electronic databases (PubMed, PsycINFO) were searched in September 2014 for randomized controlled trials (RCT). All RCTs assessed the efficacy of prazosin in the treatment of nightmares and sleep disturbances in adults with PTSS. Of the 102 articles that met selection criteria, six were retained for review. Two authors independently extracted data for nightmare frequency and intensity, sleep quality, illness severity, and blood pressure change. RESULTS: Prazosin was more effective than placebo in improving nightmares (SMD of 0.97, 95% CI 0.47, 1.47, p = 0.000), sleep quality (SMD of 0.93, 95% CI -0.2, 1.88, p=0.054 and SMD of 1.1, 95% CI of 0.21, 1.99, p = 0.02), and illness severity (SMD of 1.15, 95% CI 0.67, 1.64, p = 0.00) and had no significant effect on systolic (SMD of -0.01, 95% CI -0.36, 0.34, p = 0.95) or diastolic blood pressure (SMD of 0.255, 95% CI -0.10, 0.61, p = 0.15). DISCUSSION: The findings of this meta-analysis are in accordance with those of multiple prior studies in demonstrating that prazosin is effective for the treatment of post-traumatic stress-related nightmares, sleep disturbances, and illness severity. Our results expand upon those of a prior meta-analysis by the inclusion of an additional RCT and differing methodology, both of which positively impacted our effect sizes (Seda et al., 2015). Further, this study demonstrates that prazosin, when used at doses as high as 15 mg, had no significant effect on blood pressure. The lack of a change in blood pressure with prazosin use in the context of PTSS has important implications because the utilization and dosing of the medication may be limited by


practitioner concern for blood pressure-related side effects. Evidence that its use was not associated with significant blood pressure change in this analysis may ease concerns about side effects.

THE IMPACT OF FLOTATION RESTRICTED ENVIRONMENTAL STIMULATION THERAPY (REST) ON HEART RATE, CORTISOL, AND PERCEIVED STRESS LEVELS. G Talley, A Jahromi, Float On LLC and Float Conference, Portland, OR, USA

Restricted Environmental Stimulation Therapy (REST) is based on reducing the external sensory inputs going to the brain, including audio, visual, and tactile. Flotation REST is a specific type of REST that involves floating in a saturated epsom salt and water solution (eliminating most gravity on the body) which is kept at a skin receptor-neutral temperature. In non-flotation REST, participants are kept in total darkness in soundproof rooms to block out audio-visual inputs. Flotation REST can have a large impact on participants, helping to reduce both chronic and acute levels of stress. Here, we discuss the general effects of flotation REST on stress, as well as the specific impact on heart rate, cortisol concentration, and perceived stress levels. During the course of a session of flotation REST, cortisol levels (measured intravenously) drop significantly. Heart rate and breath rate drop off as well, as the session naturally elicits the relaxation response in participants. Perceived reduction in stress levels generally lasts well after the float session, from several hours to several days. In addition, pilot results from fMRI studies on flotation REST (currently performed at the Laureate Brain Institute in Tulsa, OK) will be discussed. RESEARCH SUPPORT: Float On LLC and Float Conference (Portland, OR, USA).

A PIVOTAL ROLE OF OREXIN (HYPOCRETIN) NEURONS IN STRESS-INDUCED THERMOGENESIS. T Kuwaki, Department of Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

Stress increases cardiac function, ventilation, and body temperature. These changes prepare the body for fight-or-flight behavior by increasing the metabolic rate, oxygen supply, and by conduction velocity of nerve impulses. A key role of one subregion of the hypothalamus, so called defense area, has long been known but precise mechanisms and/or subserving neurotransmitters remain largely unknown. Our recent research results shed light on orexin (hypocretin) neurons as a master switch that triggers multiple components of the fight-or-flight (defense) response (Kuwaki and Zhang, 2010). As an extension of this research, we suggested that the stress-induced hyperthermia would also depend on orexin. We used handling stress model in which a temperature probe was repetitively inserted into the animals rectum. We found, contrary to our expectations, orexin neuron-ablated mice (ORX-AB) but not orexin knockout mice (ORX-KO) have a blunted stress-induced hyperthermia. The brown adipose tissue, which is a major thermogenic organ in rodents, did not respond to handling stress although it did respond to a direct pharmacologic stimulation. These abnormalities in ORX-AB were not observed in ORX-KO in which orexin peptide is deficient but neurons are preserved. In wild-type mice and ORX-KO, handling stress activated orexin neurons (as revealed by increased expression of c-Fos) and the resultant hyperthermia was largely blunted by pretreatment with a beta-3 antagonist. These observation further supports the notion that attenuated stress-induced hyperthermia in ORX-AB mice was caused by a loss of orexin neurons and abnormal BAT regulation. A similar abnormality in ORX-AB but not in ORX-KO was observed when other types of stressors, namely cold (but not hot) exposure and central administration of prostaglandin E2, were applied. Therefore, the integrity (orexin and co-existing other neurotransmitter/modulators) of the orexin neurons is indispensable for full expression of multiple facets of the fight-or-flight response including thermogenesis, irrespective of the stressor types so far examined.

EFFECT OF STRESS ASSOCIATED NEUROTRANSMITTERS ON THE MEDIODORSAL PREFRONTAL CORTEX. B Nagy, I Szab, B Csetnyi, E Hormay, Z Kardi, University of Pcs, Medical School, Institute of Physiology, Pcs, Hungary

INTRODUCTION: The mediodorsal prefrontal cortex (mdPFC), constituent of the forebrain glucose-monitoring (GM) system and a major behavioral regulator, plays important role in the control of stress responses. The GM neurons are intimately involved in regulatory functions, such as ingestive behavior, taste perception and metabolism. Mild stressors increase the extracellular concentration of dopamine (DA), noradrenaline (NA) and acetylcholine (Ach) in the PFC. Little is known, however, about the neurochemical


sensitivity of neurons located in this area. Our research focuses on stress associated neurochemical characteristics, especially glucose, DA, NA and Ach sensitivities of mdPFC neurons. METHODS: In the present study, extracellular single neuron activity of the mdPFC of anesthetized rats was recorded by means of multi-barreled glass microelectrodes during microelectrophoretic administration of D-glucose, DA, NA and Ach. RESULTS AND DISCUSSION: 25% of the mdPFC cells, the GM neurons, displayed firing rate changes to microiontophoretic administration of D-glucose. DA responsiveness of the GM cells (41.2%) was significantly higher than that of the glucose-insensitive (GIS) units (16.2%). One fifth of the neurons tested changed activity to microiontophoretic application of NA, responsiveness of the GM cells to this catecholamine also proved to be significantly higher than that of the GIS units. Microiontophoretic application of Ach resulted in activity changes of more than 40% of the mdPFC neurons, with similar proportion of GM and GIS Ach sensitive cells. The characteristic DA and NA sensitivities of GM neurons in the mdPFC may have particular significance in the organization of adaptive behavioral responses to stressful and other environmental challenges. RESEARCH SUPPORT: This research was supported by the Campus Hungary Programme, Ajinomoto 51064/2009 and PTE OK KA 2013/34039/1.

EFFECTS OF AIR TRAVEL STRESS ON THE CANINE MICROBIOME A PILOT STUDY. EB Venable, SD Bland, HD Holscher, KS Swanson, Department of Animal Science Food and Nutrition, Southern Illinois University, Department of Animal Sciences, University of Illinois at Urbana-Champaign, IL, USA

INTRODUCTION: Travel stress in companion dogs is associated with diarrhea, but is poorly understood in working canines. Behavior assessment is commonly used to identify those canines which may have a higher threshold for environmental stressors, but no work has been done establishing a connection between behavior (as indicated by search performance) and travel stress (as indicated by fecal scores and microbiome stability). METHODS: Six canines (aged 18 months to 8 years), trained according to the standard established by the Federal Emergency Management Agency (FEMA), were utilized to test the effects of airline travel stress on working canines. Institutional Animal Care and Use Committee approval (#14-005) was obtained prior to the initiation of the study. All dogs were assessed for body condition score (BCS) at 4.5 0.5. Our objectives were to test the hypotheses that 1) working canines can overcome air travel stress with little or no impact on their performance, and 2) that the fecal score and subsequent microbial profile is impacted by airline travel stress. Two groups of dogs (3/group) were randomly selected from FEMA canine teams rostered in New York City, NY (CONTROL) and in Miami, FL (TRAVEL). Dogs from the TRAVEL group were flown in cabin on a commercial airline to New York (2.5-h flight time) and blood and fecal samples were collected each morning prior to travel (d 1) and search work (d 2-4). Complete blood chemistry panels were performed (VetScan 2, Abaxis Inc.). Fecal bacterial DNA was extracted (Mo Bio DNA Extraction Kits) and 16S rRNA amplicon sequencing was performed (Illumina, MiSeq) followed by bioinformatics analysis using QIIME 1.8.0. Data were analyzed using SAS (version 9.2; SAS Institute, Inc.). Significance was established at (P < 0.05). Fecal scores were assessed daily (Purina Fecal Scoring System, Nestle-Purina, St. Louis MO). RESULTS AND DISCUSSION: Fecal scores from TRAVEL were significantly higher than control (P = 0.01). BUN for the TRAVEL group was significantly higher than the CONTROL group (P = 0.01), which may be a result of the dehydration often observed in canines during travel. There was no effect of treatment on creatinine (P > 0.05). Principal coordinates analysis (PCoA) of UniFrac distances between samples based on their 97% OTU composition indicated that TRAVEL bacterial communities (P = 0.01) and bacterial community abundances (P = 0.02) were significantly different from CONTROL. Search performance (as reported by FEMA certified handlers) was not impacted by travel. These data demonstrate that airline travel of 2.5 hours impacts the working canine gut microbiota, but has no impact on working canine performance. Further work is needed to identify the physiological impact of the microbiological shifts on the canine gut. RESEARCH SUPPORT: This research was funded by Southern Illinois University.

AN FMRI ANALYSIS OF CORTISOL AND CENTRAL SENSITIZATION: PRELIMINARY EVIDENCE FOR CORTISOL-INDUCED NEUROPLASTIC ALTERATIONS THAT MAY CONTRIBUTE TO THE TRANSITION FROM ACUTE TO CHRONIC PAIN. KE Hannibal, MD Bishop, University of Florida, Gainesville, Florida

Activity-dependent facilitation of glutamate-mediated excitatory postsynaptic potentials (EPSPs) and upregulation of brain-derived neurotrophic factor (BDNF) during central sensitization may augment synaptic plasticity and potentiate long-term neuroplastic alterations in pain circuitry. Cortisol secretion may facilitate


persistent central sensitization and neuroplasticity by increasing glutamate and its NMDA receptors, prolonging calcium uptake, and upregulating BDNF and other neurotrophic factors. Similarly, cortisol secretion during an acute pain experience may potentiate neuroplastic alterations in pain circuitry that may underlie the transition from acute to chronic pain. This preliminary study analyzes the relationship between cortisol and increases in central sensitization during a minor episode of acute musculoskeletal pain. METHODS: 9 pain-free volunteers between 20-25 years old underwent a validated exercise protocol designed to induce delayed-onset muscle soreness (DOMS) to the lower back musculature. Central sensitization was assessed using fMRI during a common measure of temporal summation (TS), whereby repeated pulses of static suprathreshold heat were applied to the bottom of the right foot. Participants were told they would be randomized to 1 of 3 manual therapy interventions designed to treat low back pain. All participants received sham intervention, and central sensitization (TS during fMRI) was reassessed immediately thereafter. Salivary cortisol was collected immediately following fMRI scans. RESULTS: Overall, salivary cortisol concentration was associated with increases in hemodynamic responsiveness (HRF) in the pain processing regions of the brain during TS as compared to rest (p


SYMPOSIUM ON BIOLOGICAL PSYCHIATRY Chairs: M Koshiba, ISBS Fellow (Japan), AV Kalueff, ISBS Fellow (USA)

INTRODUCTION: PROFESSOR IZYASLAV (SLAVA) P LAPIN

This regular ISBS symposium is dedicated to Professor Izyaslav (Slava) P. Lapin (1930-2012), one of the true pioneers of experimental neuropsychopharmacology. He graduated from Pavlov Medical School in St. Petersburg, and shortly after receiving PhD, was invited in 1960 to establish the first psychopharmacology laboratory at the Bekhterev Psychoneurological Institute. The most important scientific contribution of Prof. Lapin was establishing the link between serotonin levels and mood-elevating (thymoleptic) action of antidepressants. He suggested that enhanced central serotoninergic tone is essential for the mood-elevating effects of antidepressants. Lapins serotonin hypothesis of antidepressant action, published in Lancet in 1969, became one the most cited papers published in this journal in the last 50 years. Lapins studies have

contributed greatly to the development of newest serotonergic antidepressants, such as SSRIs, currently representing the most prescribed group of psychotropic drugs in the world. Prof. Lapin was also the first to report the neuroactive effects of kynurenine and its derivatives a discovery that opened another rapidly expanding area of glutamatergic psychopharmacology. A talented professional musician, prolific writer, painter, and an enthusiastic athlete, Prof. Lapin was a strong supporter of ISBS, and generously shared his knowledge at our Stress and Behavior conferences and ISBS summer schools. His enthusiasm, friendship, generous support of junior colleagues, and the deep knowledge as both a clinical and experimental neuropharmacologist (humanists and animalists, as he called them), made a long-lasting impact on his colleagues and students.

THE EFFECT OF DEXMEDETOMIDINE ON MORPHINE-INDUCED DEPENDENCE IN RATS. TB Uskur, MA Barlas, AG Akkan, Istanbul University, Faculty of Medicine Cerrahpasa, Medical Pharmacology, Istanbul, Turkey

OBJECTIVES: Numerous studies, indicated that alpha-adrenergic system may interact with the opioid system. So, the present study was designed to investigate the effect of alpha adrenoceptor agonist Dexmedetomidine on Morphine dependent rats and its potential as drug abuse by using conditioned place preference (CPP) test. METHODS: In the following study, all groups were evaluated for reinforcement and rewarding effects by using conditioned place preference test. Male Wister Albino rats weighing 250-300 g were used in the experiment. The animals were divided into six groups as follows: 1. Control (Physiological Serum), 2. 10 mg/kg morphine, 3. 10 g/kg dexmedetomidine, 4. 20 g/kg dexmedetomidine, 5. 10 g/kg dexmedetomidine + 10 mg/kg morphine, 6. 20 g/kg dexmedetomidine + 10 mg/kg morphine. The experiment was counducted for the total period of 13 days with 4 different stages; habituation, pretest, conditioning and preference test. Conditioning phase was followed for 10 days, 4 days conditioning, 2 days rest and again 4 days conditioning. In the test phase, the rewarding effects were evaluated. Statistical analysis was done by using one way analysis of variance (one way ANOVA) followed by Newman-Keuls. RESULTS: Morphine significantly enhanced the preference scores in the drug paired side (p


SELF-OBSERVATION, REFLECTION AND COPING WITH BRAIN CHEMISTRY IN ADOLESCENT COMPETING TENNIS PLAYERS. PW Wightman, H Anselmi, Argentina National Training Center Elite Athletes, University L Zamora, Lomas Zamora, Argentina

INTRODUCTION: Adolescent rapid growth changes, including physiological, psychological, cognitive and behavioral changes, can often be seen in sport environments and surrounding social situations. Although the emotions and demands most often cause tension, anxiety and stress, idiographic sport-specific studies show that athletes not always experience these challenges as negative reactions, but may benefit from these stimuli as they produce energizing behaviors (Terry, 2013), and thus improve performance. Mental repercussions due to male and female differences are also important (Brizendine, 2007). The aim of this study is to detect emotions in competition, register them and identify their effects on performance. Players were taught to reflect, express, modify or preserve and control these mood states with the help of professionals. METHODS: Design: Qualitative/descriptive. Fifteen high-level ITF tennis players 12-17 years old (5 girls and 10 boys), 5 male players who participated in International junior tournaments, Orange Bowl and Prince Cup in 2013 and 2014. Procedures involved: Recall of emotions and autonomic symptom associated with best and worst performance (according to Goulds (2010) adaption of Orlicks (1986) Competitive Reflection Form), STAI, POMS, and semi-directed interviews. CONCLUSIONS: The mood states of 8 subjects (>50%) were fear and anger during competition, albeit subjects also perceived that, sometimes and not always, they performed better in training than in competition. This conclusion was especially considered, and although physical and technical growth contributed to diminishing negative moods, we conclude that the follow-up with psychological assessment helped (during the two years) to improve mood, performances and observed behavior.

ASSESSING GENDER DIFFERENCE IN AGGRESSION AMONG AUTISTIC CHILDRENS PARENTS. R Mittal, Civil Hospital, Moga, Punjab, India

The study was conducted to access the gender difference in aggression among the autistic childrens parents. Random sampling technique was used and 25 pair of parents (25 males + 25 females), total 50 respondents constituted the sample of study. The Consumable Booklet of A.S by Drs Guru Pyari Mathur and Raj Kumari Bhatnagar was used as a tool, consisting of 55 statements related to behavior characteristics which the subjects demonstrate in different situations. The t-test was used for statistical analyses. The mean score and t-score of males were, respectively, 187.37 and 1.07. The mean score and t-score of females were, respectively, 193.3 and 5.65. We found that autistic childrens mothers were more aggressive than fathers due to their over-loaded work extra care, emotional attachment to their children, societal and domestic pressure as well as social/economic status.

TELOMERASE DYSREGULATION IN THE HIPPOCAMPUS OF A RAT MODEL OF DEPRESSION. NORMALIZATION BY LITHIUM. Y Wei, L Backlund, G Wegener, A Mathe, C Lavebratt, Neurogenetics Unit, Center for Molecular Medicine (CMM), Karolinska University Hospital, Stockholm, Sweden

INTRODUCTION: Telomeres are protective DNA-protein complexes at the ends of each chromosome, maintained primarily by the enzyme telomerase. Shortening of the blood leukocyte telomeres (LT) is associated with aging, several chronic diseases and stress, e.g. major depression. Hippocampus is pivotal in the regulation of cognition and mood and the main brain region of telomerase activity. Whether there is telomere dysfunction in the hippocampus of depressed subjects is unknown. Lithium, used in the treatment and relapse prevention of mood disorders, was found to protect against LT shortening in humans, but the mechanism has not been elucidated. To answer the questions whether telomeres are shortened and the telomerase activity changed in the hippocampus and whether lithium could reverse the process, we used a genetic model of depression, the Flinders Sensitive Line (FSL) rat and treated the animals with lithium. METHODS: Telomere length (TL), telomerase reverse transcriptase (Tert) expression,telomerase activity and putative mediators of telomerase activity were investigated in the hippocampus of these animals. RESULTS AND DISCUSSION: The nave FSL had shorter TL, downregulated Tert expression, reduced BDNF levels and telomerase activity compared with the Flinders Resistant Line (FRL) controls. Lithium treatment normalized the Tert expression and telomerase activity in the FSL, and upregulated -catenin. This is the first report showing telomere dysregulation in hippocampus of a well-defined depression model and restorative effects of lithium treatment. If replicated in other models of mood disorder, the findings will contribute to understanding both the telomere function and the mechanism of lithium action in hippocampus


of depressed patients. FUNDING: This study was supported by grants from the Karolinska Institutet, the Swedish Medical Research Council (grants 2010-3631 CL and 10414 AAM), the Sderstrm-Knigska Foundation, the Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet, the Danish Medical Research Council and the Lundbeck Foundation.

PROTEIN BASED DIAGNOSTIC BIOMARKERS FOR EARLY DIAGNOSIS OF ALZHEIMERS DISEASE. DP Katare, RJ Mani, Center of Medical Biotechnology, Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India

INTRODUCTION: Alzheimers disease (AD) is one of the most common neurodegenerative disorders that frequently cause dementia and affect the middle-to-old aged individuals over the age of 65. AD is a complex progressive condition that involves sequentially interacting pathological cascades, including the interaction of amyloid-beta aggregation with plaque development, and the hyper-phosphorylation and aggregation of tau protein with formation of tangles. Together with associated processes, such as inflammation and oxidative stress, these pathological cascades contribute to loss of synaptic integrity and progressive neurodegeneration. Brain has multiple sources of ROS, and it cannot reduce oxidative stress by itself. Today the focus is being placed on the discovery of oxidative stress biomarkers to study the increased oxidative damage during disease progression. Inadequacy in disease detection/treatment and the lack of diagnostic and prognostic tools have prompted investigators to turn to proteomics-based biomarker discovery. Although an emerging field proteomics application promise to uncover biomarkers critical for differentiating patients with neurodegenerative diseases from healthy people and from patients affected by other diseases. These studies will also contribute mechanistic information to facilitate identification of new drug targets for subsequent therapeutic development. In the present study, an animal model of AD was developed in zebrafish and Wistar rats, and the differential expression of proteins was analyzed in serum and brain tissue with the disease progression. METHODS: The animal model in zebra fish and male Wistar rats was developed using STZ toxicant. Behavioral studies like Morris water maize, Tail suspension, novel object identification, light and dark test were carried out. Biochemical analysis of enzymes of oxidative stress like Catalase, LPO, SOD etc were done in serum and brain tissue. Next, serum proteins were screened at regular time intervals of disease progression by 1D SDS PAGE and 2 D Electrophoresis followed by MALDI-TOF-MS to see the protein expression changes. RESULTS AND DISCUSSION: The behavior studies and biochemical analysis confirmed AD in the animal model. The analysis of proteins identified some low molecular weight proteins and some proteins involve in oxidative stress, which were subjected to further validation for the prospective diagnostic biomarkers. Further characterization of these proteins will likely shed more light on the mechanisms by which the changes or modification in these proteins and their interaction with the other protein in the pathway contribute to the development of AD. RESEARCH SUPPORT: Infrastructure support provided by Amity University Uttar Pradesh Noida.

Afternoon session


INTERACTIVE POSTER SESSION

DO SINGLE EXPERIENCES OF CHILDHOOD ABUSE INCREASE DEPRESSION AND ANXIETY SYMPTOMS IN ADULTHOOD? W Rehan, A Johansson, P Santtila, Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland

INTRODUCTION: Evidence suggests that abuse experiences in childhood increase the risk for development of depression and anxiety disorders in adulthood. However, no previous studies have looked at the effects of single abuse experiences. In the present study, we explored the effects of such experiences compared to no abuse experiences and to repetitive abuse experiences on depression and anxiety symptoms in adulthood. METHODS: We used a population-based sample of 10980 participants (3766 male and 7214 female twins and their siblings). The mean age of the men was 29.2 (SD = 7.4) and of the women 28.8 (SD = 7.2) years. The participants reported on their abuse experiences using the Childhood Trauma Questionnaire (CTQ) and on their current depression and anxiety symptoms using the Brief Symptom Inventory-18 (BSI-18). RESULTS AND DISCUSSION: We found that in both men and women even single experiences of abuse were associated with the development of increased adult depression and anxiety symptoms compared to no abuse experiences when looking at the different abuse types independently, with the exception that in men a single experience of physical abuse did not lead to increases in either anxiety and depression symptoms. Also, as expected, repeated experiences of abuse increased both anxiety and depression symptoms compared to a single experience. However, when we isolated the individuals who had only had a single experience of any type abuse, no increases in anxiety were found compared to those with no experiences with the exception of depression in women. These findings suggest that in both men and women that even single experiences of especially psychological abuse can have long-lasting negative consequences. However, this is mostly explained by comorbidity between abuse types with the exception of women who seem to be suggestible to increases in depression from a single experience of abuse in the absence of any other types of abuse. RESEARCH SUPPORT: This research was supported by the Academy of Finland Grant 210298, a Center of Excellence grant from the Stiftelsen fr bo Akademi Foundation Grant 21/22/05.

COMPARING PSYCHOLOGICAL MORBIDITY AMONG STUDENTS APPEARING FOR FINAL PROFESSIONAL MBBS EXAMINATION AND CIVIL SERVICES EXAMINATION. A Sharma, M Singla, BS Sidhu, Department of Psychiatry, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India

BACKGROUND: Present educational system is most competitive and lesser opportunities in educational institutes and services later on. High expectations of family and future insecurities among students force them to take pressure of competitive exams beyond their compromised abilities by various factors. This leads to psychiatric problems among students at very young age. This study aimed to compare psychiatric morbidity in students appearing for civil services and final year MBBS examination. MATERIAL AND METHOD: Two study groups of students for preliminary and mains examinations of civil services were made and later divided into repeaters and fresher students in each. Students were subjected to structured and standardized PGI-HQ 1 and SCL-80 scales to assess psychiatric morbidity. Data was collected and later analyzed using chi square and p value. RESULTS: Clinical diagnosis on ICD-10 revealed that significantly more (p


INTRODUCTION: Arginine vasopressin (AVP) plays a role in social behavior, through receptor AVPR1A. The promoter polymorphism AVPR1A RS3 has been associated with human social behaviors, and with acute response to stress. Here, the relationships between AVPR1A RS3, early-life stressors, and social interaction in adulthood were explored. METHODS: Adult individuals from a Swedish population-based cohort (n=1871) were assessed for self-reported availability of social integration and social attachment and for experience of childhood adversities. Their DNA samples were genotyped for the microsatellite AVPR1A RS3. RESULTS AND DISCUSSION: Among males, particularly those homozygous for the long alleles of AVPR1A RS3 were vulnerable to childhood adversity for their social attachment in adulthood. A similar vulnerability to childhood adversity among long allele carriers was found on adulthood social integration, but here both males and females were influenced. CONCLUSIONS: Early-life stress influences the relationship between AVPR1A genetic variants and social interaction. For social attachment, AVPR1A is of importance in males only. The findings add to previous reports on higher acute vulnerability to stress in persons with long AVPR1A RS3 alleles and increased AVP levels. RESEARCH SUPPORT: This work was supported by the Swedish Research Council (2009-5546 YF, 2010-3631 CL), the China Scholarship Council, the Karolinska Institutets Faculty Funds, and the Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet (SLL20110560 CL, 20090281 YF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the publication.

EFFECTS OF MOBILE TECHNOLOGY USE ON MOOD AND BODY MASS INDEX. CB Shay, C Hansen, Keiser University, Ft. Lauderdale, FL, USA

Technology has advanced rapidly in the last decade, especially relating to individual mobile computing technologies such as smartphones and tablets. Prior research found conflicting results regarding psychological and physiological effects of these new technologies. This study (n=487) examined effects mobile technology use had on stress, anxiety, and depression, as defined by the Depression Anxiety Stress Scale-21 (DASS-21), as well as the effect of technology use on Body Mass Index (BMI). The DASS-21 was combined with a modified version of a technology-use measure formulated by Wack and Tantleff-Dunn (2009) to determine possible effects of electronic gameplay on BMI. Data were gathered using Amazons Mechanical Turk (AMT), a crowd sourcing online service. Results suggest there might be a relationship between stress in males and higher levels of technology use (here defined as the total of daily time spent video gaming, in general PC/Internet use, tablet use, and smartphone use). In women, all three of the DASS-21 subscales showed significant correlation between higher levels of technology use and higher levels of stress, depression and anxiety. A small correlation between unhealthy levels of BMI and technology use, including Smartphone and tablet use, was also observed.

AMYGDALA INVOLVEMENT IN AVOIDANCE ACQUISITION IN A BEHAVIORALLY INHIBITED RAT STRAIN. DP Miller, KM Moench, KCH Pang, RJ Servatius, Carthage College, Kenosha, WI, Stress and Motivated Behavior Institute, Newark, NJ, Department of Veterans Affairs, NJ Healthcare System, East Orange, NJ, NJ Medical School, Rutgers University, Newark, NJ, USA

INTRODUCTION: Behavioral inhibition is an important risk factor for the development of anxiety disorders. The amygdala has been demonstrated to be critical for fear conditioning, and thus it has been suggested that anxiety disorders can be understood simply by the study of fear conditioning. We have suggested that the critical nature of avoidance in anxiety disorders requires the study of avoidance in animal models as well (Servatius et al., 2008). We use the behaviorally inhibited Wistar Kyoto (WKY) rat in comparison to the outbred Sprague Dawley (SD) strain. Our avoidance paradigm is signaled leverpress, a non-species specific defense response (non-SSDR) that requires autoshaping during training. We tested the hypothesis that the basolateral amygdala is necessary for avoidance acquisition while systematically varying the contingency between the warning signal and avoidance responding. METHODS: In the first experiment an avoidance leverpress immediately terminated the warning signal and resulted in no shock delivery. In the second experiment, the warning signal remained on for 1 min regardless of the rats behavior. Thus the negative reinforcement of the prevention of shock delivery was not immediately contingent upon avoidance lever pressing. Bilateral electrolytic lesion of the basolateral amygdala and lesion histology was performed similar to (Lee and Kim, 2004). Escape, avoidance and inter-trial responses were recorded. RESULTS AND DISCUSSION: Both learning contingency and behavioral inhibition affected whether basolateral amygdala


lesions disrupted avoidance acquisition. While lesioned WKY rats showed avoidance acquisition deficits in both protocols, avoidance acquisition was not disrupted in SD rats in the non-contingent protocol. Our data support the importance of a diathesis model that takes into account key vulnerabilities that are predictive of anxiety pathology. These data also demonstrate that manipulations of the learning context allow the observation of differences in both learning and neural function in vulnerable populations. RESEARCH SUPPORT: This research was supported by the Stress and Motivated Behavior Institute, UMDNJ (USA).

EEG BIOFEEDBACK AND LAVENDER AROMATHERAPY IN MIGRAINE - A PRELIMINARY STUDY. HH Bauer, SM Nagel, College of Human Medicine, Michigan State University, East Lansing, MI; Department of Psychology, Saginaw Valley State University, University Center, MI, USA

INTRODUCTION: Migraine is a common medical condition that is often linked to stress. Two relaxation techniques, electroencephalographic (EEG) biofeedback and lavender aromatherapy may reduce migraine severity. The present study tested the hypothesis that migraineurs would experience greater relaxation when simultaneously exposed to lavender aromatherapy and EEG biofeedback than in response to EEG biofeedback alone. METHODS: Twenty-two individuals with a chronic history of migraine were recruited using IRB approved methods. They were assessed on the level of important moderator variables, a self-report, mood state questionnaire (Profile of Mood States (POMS)), and EEG Biofeedback Training with (WL) or without (WoL) Lavender Aromatherapy. Raw EEG data (FPZ) were subjected to spectral analysis, and the power within beta, alpha and theta bandwidths were compared. Slower EEG power indicated greater relaxation. RESULTS AND DISCUSSION: The WL condition tended to increase positive mood states over the WoL condition (t=-1.9(df=13), p=0.07). Lavender aromatherapy, therefore, tended to increase a positive subjective mood in the participants, while EEG biofeedback did not. Individuals in the WoL condition tended to experience more relaxation as measured by theta power during the biofeedback training, while the same was true for individuals in the WL condition during the segment following biofeedback, when they were only exposed to lavender (F(1,18)=3.4, p=0.08). One speculation offered to account for this trend is that the two relaxation techniques interfere with each other when used simultaneously. As these methods work through different mechanisms, it is suspected that they work better alone than together. Furthermore, as the WoL condition showed greater variance in subjective mood (F(1,18)=9.1, p


(FIRM) Grant 10/RD/TMFRC/709, the Alimentary Pharmabiotic Centre (APC) grants 07/CE/B1368 and 12/RC/2273, and the Science Foundation Ireland grant 12/IA/1537.

THE USE OF MODERN TECHNOLOGY DURING TRAINING OF COGNITIVE PROCESSES. M Zubanska, A Bonus-Dziego, AK Zubrzycka, Police Academy in Szczytno, Szczytno, Poland

In December 2012, Police Academy in Szczytno (Poland) initiated a research project Development of Training Interactive Psycho-Stimulator for the Police, in order to develop and implement an innovative diagnostic system for the evaluation of training and competence of cognitive stimulation and psychomotor skills of police officers. The key tasks of the project include the development of a set of psychological tests to assess and monitor the psychomotor performance and selected cognitive processes; the development of a set of computer games that stimulate the development of selected cognitive processes; the development of a psychophysiological recorder to aid training. The diagnostic system for the evaluation of training and stimulation of cognitive competence that is being developed consists of three interconnected modules: diagnostic, training module and knowledge base, within a fully functional web-based platform. Diagnostic module consists of the four components, each representing a set of psychological tests for independent measurement of the level of concentration, perception, working memory and analytical thinking. The developed psychological tests are characterized by internal compliance at the level of 0.60. The training module is a set of games related to the stimulation of cognitive competence, allowing for online training, using both PCs and mobile devices as smart phones or tablets. Implementation of the system on the online platform will allow users to obtain feedback on their training progress in real-time, and to compete with each other. Knowledge base (i.e. the last module of the system) provides information and articles on the development of cognitive functions. On the basis of psychological tests, we have designed short tests for rapid diagnosis of cognitive and psychomotor skills and for determining the level of preparedness in the area of the measured components to work in particularly difficult situations. As part of the project, a psychophysiological recorder is also designed for training to cope with stress by using information on the physiological reactions occurring during both games and solving tests.

ENRICHED ENVIRONMENT DECREASED ANXIETY-RELATED BEHAVIOR IN AN ANIMAL MODEL OF GENERALIZED ANXIETY DISORDER. GP Dias, ACD Silveira, MCN Bevilaqua, AA Marques, G Cocks, J Landeira-Fernandez, S Thuret, AE Nardi, Universidade Federal do Rio de Janeiro UFRJ; Pontifcia Universidade Catlica, Rio de Janeiro, Brazil; Kings College London, London, UK

INTRODUCTION: Anxiety is a complex psychobiological process which often emerges after experiences perceived as threatening. If the anxious responses are excessive in magnitude or frequency, or if they occur in the absence of stressors, it can give rise to a pathological condition, such as generalized anxiety disorder (GAD). In a previous report, we described some of the behavioral characteristics of an animal model for the study of GAD, the Carioca High Conditioned Freezing rats (CHF). This model was generated after the selection of Wistar rats with higher freezing in contextual fear conditioning. We verified that these animals present higher anxiety in the elevated plus maze (EPM) and decreased social interaction, with no differences in depressive-related behavior or in the object recognition test. We also showed that these animals present increased serum corticosterone, decreased number of neuroblasts in the hippocampus, as well as increased expression of hippocampal brain-derived neurotrophic factor and dendritic spines. However, the search for interventions that could potentially modulate these aspects and restore behavior had yet to be done. For this purpose, we investigated here the effects of the enriched environment (EE) on the anxious behavior of CHF and control rats. METHODS: 2-month old males were submitted to the EE for 2 months. The EE consisted of a larger cage, with 12 animals per cage for increased social interaction and with the presence of stimulating toys and platforms. After the 2-month period in the EE, the animals were subjected to a single 5-minute trial in the EPM. RESULTS AND DISCUSSION: The time CHF-EE rats spent in the open arms of the EPM was significantly increased in comparison with CHF rats and similar to that of control and control-EE animals. Although further behavioral testing is needed in other paradigms, we observed that the EE in adulthood can be a potentially effective intervention to restore the anxious behavior in our model. RESEARCH SUPPORT: This study was supported by Research Foundation of the State of Rio de Janeiro (FAPERJ-Brazil), National Council for Scientific and Technological Development (CNPq-Brazil).


INCREASED RISK OF SEXUALLY TRANSMITTED DISEASES AFTER BEREAVEMENT A SWEDISH NATIONAL COHORT. E Bond, D Lu, E Herweijer, K Sundstrom, U Valdimarsdottir, K Fall, LA Dahlstrom, P Sparn, F Fang, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

INTRODUCTON: Although inconclusive, evidence has started to accumulate suggesting a link between psychological stress and cervical cancer. However, none of the previous studies has addressed potential underlying pathways, for instance increased sexual risk behavior or compromised immune surveillance. Therefore we aimed to assess the relationship between bereavement, as a proxy for severe psychological stress, and the risk of sexually transmitted diseases (STDs). METHODS: We conducted a population-based cohort study from 1987 to 2012 using the Swedish Multi-Generation Register, including 3,002,209 women at the age of 10- 44 years who were born in Sweden and had at least one parent recorded in the Register. Exposure was defined as death of a first degree relative (child, parent or sibling) or spouse before 1987 or during the study (N=979,579, 33%). STDs were defined as hospital visits, either inpatient or outpatient, with a STD as main or secondary discharge diagnosis, including condyloma, gonorrhea, chlamydia, syphilis, human immunodeficiency virus-1, and genital herpes simplex. Poisson regression was used to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of STDs, comparing the incidence rates of women who had lost a close relative to those who had not. RESULTS AND DISCUSSION: When compared to women without bereavement, bereaved women were at significantly higher risk of nearly all STDs studied. The associations appeared slightly stronger for inpatient hospital contact for STDs; for condyloma for example the IRR was 1.18 (95% CI: 1.08-1.30) for inpatient and 1.06 (95% CI: 1.00-1.13) for any hospital contact. In contrast, the IRRs of acute salpingitis a severe complication of STDs, did not vary between inpatient contact (1.28; 95% CI: 1.13-1.44) and any hospital contact (1.27; 95% CI: 1.16-1.38). Our findings indicate an increased risk of receiving an STD diagnosis after bereavement. While we do believe that this is mainly due to behavioral changes, the stronger findings on inpatient hospital contact for STDs, as well as for acute salpingitis a complication of STDs, do suggest that immune modulatory effects of the stressful life event might also play a role. RESEARCH SUPPORT: This research was supported by the Swedish Society for Medical Research.

THE CYSTIN/GLUTAMATE ANTIPORTER AS A POTENTIAL NOVEL TARGET TO MODULATE THE STRESS RESPONSE? T Demuyser, E Bentea, L Deneyer, G Albertini, J Van Liefferinge, E Merckx, A Massie, I Smolders, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium

INTRODUCTION: In modern society, stress is a major causative factor for a variety of psychiatric disorders. Depression, one of the main causes of disability worldwide, is a multimodal disease with chronic stress considered as a trigger for depressive episodes. Depression and comorbid anxiety are usually related to a malfunctioning monoaminergic system, nowadays however compelling evidence points at an important role of glutamate in the etiology of the depressed/anxious brain. Being the major excitatory neurotransmitter in the central nervous system, glutamate can potentially have important excitotoxic effects. System xc- is the cystine/glutamate antiporter and the major source of extrasynaptic glutamate in some important depression-related brain areas, where it can be an interesting new target for improved psychopharmacological treatment. METHODS: In this study we investigated the effect of loss of functional system xc- (e.g. deletion of the specific light chain subunit xCT; xCT-/-), on chronic stress induced depression and anxiety in a validated animal model. Therefore, we subjected xCT-/- and +/+ mice, treated with chronic corticosterone injections (excessive chronic stress), to a battery of acute stress-based tests for depressive- and anxiety- like behavior, and compared their behavior to vehicle-treated and nave animals. RESULTS AND DISCUSSION: Interestingly we found decreased depressive- and anxiety- like behavior in the nave xCT-/- mice in all of the tests conducted. Unexpectedly however the decrease in depressive- and anxiety-like behavior faded and disappeared after vehicle and corticosterone treatment. These findings support further research for the role of system xc- in the stress response, since the involvement of the antiporter in regulating the response to acute versus chronic stress seems to differ. RESEARCH SUPPORT: This research was supported by the Fund for Scientific Research Flanders (FWO, grant G.038412N), the Queen Elisabeth Medical Foundation (GSKE), and the Vrije Universiteit Brussel (Strategic Research Program, grant SRP40).

SEEKING SAFETY: A RANDOMIZED CLINICAL TRIAL. C Hansen, D Hien, Keiser University, Ft. Lauderdale, FL, Columbia University, City College of New York, NY, USA


INTRODUCTION: Women who seek treatment for substance use disorders are more than twice as likely to have co-occurring PTSD than men, yet few specific therapies have been developed that integrate treatment of these co-occurring disorders. Furthermore, many treatment professionals fear that integrating PTSD intervention may cause adverse reactions that could undermine the substance abuse treatment. The purpose of this study was to test the effectiveness of Seeking Safety, a cognitive-behavioral integrated group treatment for PTSD and substance use disorders, in a multi-site, national controlled clinical trial among women enrolled in intensive outpatient substance abuse treatment in community-based treatment centers. METHOD: Seeking Safety was compared to a Womens Health Education control as an adjunct to regular treatment for women with co-occurring diagnoses enrolled in community treatment centers. A total of 353 women from seven treatment centers were randomized in a National Institutes for Drug Abuse Clinical Trials Network nationwide study. RESULTS AND DISCUSSION: Participants in both treatment conditions demonstrated significant improvement in PTSD symptoms over the six-week course of treatment as well as during the year-long follow-up period; however, there were no significant differences between conditions. Substance use, measured by abstinence as well as number of days of use per week, did not improve significantly over the course of the study, and no significant differences were found between groups. Results support the value of integrating PTSD treatment for those with co-occurring disorders, and further refinement of treatment is indicated in order to improve substance use outcomes. RESEARCH SUPPORT: This research was supported by grants from the National Institute on Drug Abuse, NIDA: U10DA13035 (EV Nunes, PI), U10 DA13714 (D Donovan, PI), U10 DA13038 (K Carroll, PI), U10DA13732 (E Somoza, PI), U10 DA13727 (K Brady, PI), U10 DA013720 (J Szapocznik, PI), U10 DA013046 (J Rotrosen, PI), and K24 DA022412 (EV Nunes). The Clinical Trial Identification Number is NCT00078156 (NIDA, NIH).

DEVELOPMENT AND IN VITRO CHARACTERIZATION OF NEUROMEDIN U ANALOGS. A De Prins, C Betti, B Sivertsen, V Caveliers, A Van Eeckhaut, B Holst, S Ballet, I Smolders, Department of Pharmaceutical Chemistry and Drug Analysis, Department of Organic Chemistry, Department of In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Brussels, Belgium; Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark

Chronic stress is a predominant risk factor for a variety of psychiatric and neurological disorders, such as depression, anxiety and epilepsy. Endogenous systems which regulate the stress response are interesting targets for the development of novel treatments for these stress-related disorders. In this study we focus on neuromedin U (NMU), a neuropeptide regulator of the stress response via top-down control of the hypothalamus-pituitary-adrenal axis. NMU exerts its biological effects via two G protein-coupled receptors, NMUR1 and NMUR2. NMUR1 is mostly found in the periphery whereas NMUR2, the receptor of our interest, is most abundant in the central nervous system. The purpose of this study is to develop new peptidergic selective NMUR2 antagonists which are enzymatically stable and blood-brain-barrier (BBB) permeable. NMU-8, a natural occurring form of NMU, is taken as lead molecule for the synthesis of new analogues. The NMU-ligands are synthesized via solid phase peptide synthesis under classical conditions on rink amide polystyrene resin. A first batch of analogues is prepared on basis of the available structure-activity relationships. The in vitro characterization of these peptides is performed by an inositol phosphate accumulation assay. The results of this in vitro characterization are generally in line with the available literature. EC50 values of a similar magnitude are found for NMU-8. Moreover our experiments revealed that acetylation of the N-terminus leads in general to an increase of the relative activity compared to the non-acetylated ligand. In conclusion, further research is needed to synthesize a NMUR2 selective, enzymatically stable and BBB permeable ligand. RESEARCH SUPPORT: This research was supported by the Agency for Innovation by Science and Technology in Flanders (IWT).

PSYCHOLOGICAL STRESS IN EARLY LIFE AFFECTS ADULT RATS IN A SEX-DEPENDENT MANNER. SR Melo, CTD Antoniazzi, S Hossain, B Kolb, State University of Maringa, Parana, Brazil

INTRODUCTION: Psychological models of stress in different phases of life in laboratory animals have been used to try to understand the adult signature of early stress in the brain and behavior. Previous studies have shown that mild stress during gestational, neonatal, and adult periods produce changes in brain and anxiety-related behavior in adulthood. In this study our goal was to study the relation between the adult behaviors and brain anatomy as a result of stress in lab rats in different phases of early life. METHODS:


Long-Evans male and female rats were stressed by maternal separation (MS) and elevated platform (EP). We compared the effect of neonatal stress in rats from postnatal days 3 to 14 (P3-14, MS) and juvenile stress (P23-34, EP) as well the combination of stressors (P3-8, MS + P23-28, EP) on the adult brain (P95). The elevated plus maze test was used to verify the anxiety-like behavior exhibited by the rats. RESULTS AND DISCUSSION: The brains of all stressed groups, males and females, were significantly smaller (brain weight) than control animals. Male but not female rats in the MS and the MS+EP groups showed increased anxiety-related behavior relative to control animals in an elevated plus maze. EP male rats were not significantly more anxious than control, in contrast to the females, which showed a reduced level of anxiety. These results suggest that in both sexes, juvenile rats are more resilient to stress than rats exposed to neonatal stress. In addition, females are more resilient to neonatal stress than males. Morphological analysis of cortical pyramidal neurons is in progress. RESEARCH SUPPORT: This research was support by Capes Brazil and NSERC of Canada.

EVENT-RELATED POTENTIALS FROM PATIENTS WITH MAJOR DEPRESSIVE DISORDER WITH MELANCHOLIC FEATURES AND ANXIOUS DISTRESS. MV Pronina, GY Poliakova, YI Poliakov, VA Ponomarev, A Mller, JD Kropotov, NP Bechtereva Institute of the Human Brain RAS, Saint-Petersburg, Russia

According to DSM-5, major depression disorder (MDD) is specified by melancholic fe

Final Program and Proceedings - 5th International Regional "Stress and Behavior" Neuroscience and...

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