Introduction

•The Sigma-1 receptor was discovered in 1976 by pharmacological studies with drug addiction model systems. More recently, it has been found to mediate the regulation of neurogenesis, memory, and drug addiction (Aydar et al., 2002; Hayashi and Su, 2001)

•The natural agonist for the Sigma-1 receptor has not been identified, but there are about 40 drugs currently being researched that activate the sigma-1 receptor.

•The Sigma-1 receptor works by a signaling cascade, when the target proteins such as BiP is activated, it can lead into decreased stress (Hayashi and Su, 2001). BiP (endoplasmic reticulum chaperone) does this by causing stress transducers to become activated, which plays a role in regulating stress levels (Penas et al., 2011).

•Increased stress levels on patients recovering from injuries are shown to have slower recovery time and pro-inflammatory responses in cell tissue (Elenkov et al., 1999). New drugs that are being released for clinical trials generally test for behavioral effects such as stress.

•PRE-084 was created to promote neuroprotection for root avulsion injuries and cause neurite elongation; to do this PRE-084 targets the Sigma-1 receptor, which should activate the stress transducers (Penas et al., 2011). This drug is still being tested in a laboratory setting using rodent models.

•An organism that has been growing more popular in behavioral studies with stress is the zebrafish. Some of the benefits of using zebrafish for behavioral studies on stress is that they are inexpensive to house and they have a sequenced genome.

Determining whether PRE-084 (2-(4-Morpholinethyl)1- Phenylcyclohexanecarboxylate) decreases stress in Zebrafish

(Danio rerio)Neil Amin

York College Department of Biological Sciences

Objectives• Does PRE-084 decrease stress in zebrafish?

• Does PRE-084 cause unusual behavior patterns in zebrafish?

Conclusion• There is a trend developing in the percent of time at

the top of the tank as the concentration of the drug increases.

• The zebrafish did not exhibit a lot of unusual behavioral patterns.

• There is not enough information to show if the zebrafish was directly affected by PRE-084 because they did not show any significant stressful behavior patterns.

• In previous studies they conducted the experiment and monitored multiple zebrafish with tracking software; in this study the sample size was small and this could have effected the data.

Future Experiments• Use a wider variety of PRE-084 concentrations• Use tracking software to analyze the behavior of the

zebrafish• Complete a cortisol extraction test

• Direct relationship between stress and cortisol levels.

Literature Cited• Aydar, E., Palmer, C.P., Klyachko, V.A., and Jackson, M.B. (2002). The sigma receptor

as a ligand-regulated auxiliary potassium channel sub- unit. Neuron 34, 399–410.

• Elenkov, I. J., & Chrousos, G. P. (1999). Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease. Trends In Endocrinology And Metabolism, 10(9), 359-368.

• Hayashi, T., and Su, T.P. (2001). Regulating ankyrin dynamics: Roles of sigma-1 receptors. Proc. Natl. Acad. Sci. USA 98, 491–496.

• Penas, C., Pascual-Font, A., Mancuso, R., Fores, J., Casas, C., & Navarro, X. (n.d). (2011). Sigma Receptor Agonist 2-(4-Morpholinethyl) 1 Phenylcyclohexanecarboxylate (Pre084) Increases GDNF and BiP Expression and Promotes Neuroprotection after Root Avulsion Injury. Journal Of Neurotrauma, 28(5), 831-840.

AcknowledgmentsSpecial thanks to Dr. Wendy Boehmler and Dr.Bradley Rehnberg for their guidance.

MethodsPretreatment (30 minutes)

45 Zebrafish

38 Liter tank(n=15) Low

Concentration

38 Liter tank(n=15)Control

38 Liter tank(n=15)

High Concentration

19 Liter tank (n=5) 3x

19 Liter tank (n=5)3x

19 Liter tank (n=5)3x

Behavioral Recording (30 mins)

Behavioral Recording (30 mins)

Behavioral Recording (30 mins)

Behavioral Analysis of recordings

http://www.nature.com/nprot/journal/v5/n11/full/nprot.2010.140.html

http://www.focusonnature.be/gallery/zebrafish

Results

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