Laborda, M. & Miller, R. (2013). Preventing Return of Fear in an Animal Model of Anxiety. Additive...

Behavior Therapy 44 (2013) 249–261www.elsevier.com/locate/bt

Preventing Return of Fear in an Animal Model of Anxiety: AdditiveEffects of Massive Extinction and Extinction in Multiple Contexts

Mario A. LabordaUniversidad de Chile

Ralph R. MillerState University of New York–Binghamton

Fear conditioning and experimental extinction have beenpresented as models of anxiety disorders and exposuretherapy, respectively. Moreover, the return of fear serves asa model of relapse after exposure therapy. Here we presenttwo experiments, with rats as subjects in a lick suppressionpreparation, in which we assessed the additive effects of twodifferent treatments to attenuate the return of fear. First, weevaluated whether two phenomena known to generatereturn of fear (i.e., spontaneous recovery and renewal)summate to produce a stronger reappearance of extin-guished fear. At test, rats evaluated outside the extinctioncontext following a long delay after extinction (i.e., adelayed context shift) exhibited greater return of extin-guished fear than rats evaluated outside the extinctioncontext alone, but return of extinguished fear following adelayed context shift did not significantly differ from thereturn of fear elicited in rats tested following a long delayafter extinction alone. Additionally, extinction in multiplecontexts and a massive extinction treatment each attenuatedthe strong return of fear produced by a delayed context shift.Moreover, the conjoint action of these treatments was

National Institute of Mental Health Grant 33881 supported thisresearch.Mario A. Labordawas supported by the ComisiónNacionalde Investigación Científica y Tecnológica (CONICYT-Chile). Theauthors would like to thank Henry Cham, Lisa Mash, GonzaloMiguez, and Cody Polack for their comments on an earlier version ofthis manuscript.

Address correspondence to Ralph R. Miller, Department ofPsychology, SUNY–Binghamton, Binghamton, NY 13902-6000;e-mail: [email protected], or Mario A. Laborda, Depart-ment of Psychology, University of Chile, Santiago, Chile; e-mail:[email protected]/44/249–261/$1.00/0© 2012 Association for Behavioral and Cognitive Therapies. Published byElsevier Ltd. All rights reserved.

significantly more successful in preventing the reappearanceof extinguished fear, suggesting that extensive cue exposureadministered in several different therapeutic settings has thepotential to reduce relapse after therapy for anxietydisorders, more than either manipulation alone.

Keywords: return of fear; massive extinction; extinction in multiplecontexts; exposure therapy; relapse

If fears and phobias are acquired through stimulipairings as associative accounts suggest (e.g., Bouton,Mineka, & Barlow, 2001; Field, 2006; Laborda &Miller, 2011; Mineka & Oehlberg, 2008), then thestudy of manipulations that reduce the expression ofthis type of association could be informative for thoseinterested in developing new techniques to treat thesebehavioral disorders (e.g., Craske et al., 2008;Laborda, Miguez, Polack, & Miller, 2012). After aconditioned stimulus (CS) has acquired behavioralcontrol through pairings with an unconditionedstimulus (US), presenting it without the US reducesits potential to elicit conditioned responding. Thisphenomenon has been labeled extinction (Pavlov,1927) and has been presented as a model of exposuretherapy (e.g., Bouton, 2000; Bouton&Nelson, 1998),which is currently considered the most successfultherapeutic approach for treating anxiety and relateddisorders (e.g., Chambless & Ollendick, 2001).Pavlov (1927) proposed that during extinction

treatment a new learning experience takes place and,after a theoretical detour in which extinction wasthought to erase memories (e.g., Rescorla&Wagner,1972), contemporary researchers have reached a

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250 laborda & miller

consensus consistent with his approach. Evidencesuggests that what is learned through extinctiontreatment is an inhibitory-like association that is mostreadily expressed in the spatiotemporal context inwhich extinction took place (for reviews, see Bouton,1993, 2000; Craske, Liao, Brown, & Vervliet, 2012;Craske et al., 2008). Among the evidence demon-strating that extinction learning involves acquisitionof a context-specific inhibitory-like association aresignature phenomena of extinction such as renewal(Bouton & Bolles, 1979) and spontaneous recovery(Pavlov), both of which indicate that originalassociations remain largely intact after extinction. Inthe case of renewal, testing outside the context ofextinction usually elicits more conditioned respond-ing than when testing occurs in the extinction context(e.g., Bouton & Bolles, 1979; Bouton & King, 1983;Laborda, Witnauer, & Miller, 2011). In the case ofspontaneous recovery, a long delay imposed betweenextinction and testing encourages the expression ofthe extinguished excitatory information rather thanthe inhibitory-like information learned during extinc-tion training (e.g., Pavlov).Evidence of the reappearance of extinguished

responding in humans has also been reported (e.g.,Effting & Kindt, 2007; Milad, Orr, Pitman, &Rauch, 2005; Neumann & Kitlertsirivatana, 2010;Vansteenwegen et al., 2005). For example, using adifferential fear conditioning preparation in whichone CS predicted the occurrence of an aversive shockand a second CS predicted no shock, Effting andKindt found stronger return of fear in participantswho were tested back in the acquisition context afterextinction in a second context (i.e.,ABA renewal; herewe use the common notation for different types ofrenewal of three successive letters in which the firstletter denotes the context of acquisition, the secondthe context of extinction, and the third the context oftesting) than in participants who received acquisition,extinction, and testing in the same context (i.e., AAAcontrol). For a recent review on the return of fear inhuman fear conditioning experiments see Vervliet,Baeyens, Van den Bergh, and Hermans (in press).Reappearance of extinguished responding can also befound in experimental studies with nonclinicalhuman samples. For example, Rodriguez, Craske,Mineka, andHladek (1999) provided support for thecontext-specificity of exposure treatment. Spider-fearful participants who were tested in the samecontext in which they previously received exposuresessions exhibited less fear response (i.e., lower heartrate level) than those participants who were treatedand tested in two different contexts. In a differentexperimental preparation, Collins and Brandon(2002) found a return of urges to drink in socialdrinkers when they were tested outside of the context

in which they received exposure sessions to alcohol-related cues.Many theoretical accounts for renewal and spon-

taneous recovery have been proposed, but presentingthem is beyond of the scope of the present researchreport (see McConnell & Miller, 2012). Here weadopt a general theoretical framework in whichextinction treatment is viewed as an example ofretroactive outcome interference. From this perspec-tive, extinction treatment forms a CS-noUS associa-tion that interfereswith the CS-US association formedduring acquisition training. Whether and to whatdegree behavior indicative of acquisition or extinctionis expressed at test depends of the comparisonbetween the reactivated US and noUS memoriesfrom acquisition and extinction. If the reactivated USmemory from acquisition, which is a product of thestrength of the CS-US association and the facilitatorycues from acquisition present at test, is stronger thanthe reactivated noUS memory from extinction, whichis a product of the strength of theCS-noUSassociationand the facilitatory cues from extinction present attest, then we expect to see strong conditionedresponding at test. Conversely, if the reactivatednoUS memory from extinction is stronger than thereactivated US memory from acquisition, we wouldexpect to see weak conditioned responding at test(Laborda &Miller, 2012; Miller & Laborda, 2011).One consequence of this logic is that the dissimi-

larities between the contexts of extinction and testingshould positively correlatewith the degree of return offear evidenced at test because fewer facilitatory cuesfrom extinction treatment are present. In terms of thepresent series, testing in a different spatiotemporalcontext should produce more reappearance ofextinguished responding than testing in a differentspatial or different temporal context alone. Using aconditioned taste aversion preparation with rats,Rosas and Bouton (1998) provided initial evidenceof summation of these two extinction-to-test contex-tual manipulations, each of which alone producessome reappearance of extinguished responding. Thiswould be expected if changes in the physical andtemporal contexts summate to produce a strongerform of return of extinguished responding. Rosas,Vila, Lugo, and López (2001) successfully extendedRosas andBouton's results to ahuman causal learningpreparation.In Experiment 1we evaluatedwhether renewal and

spontaneous recovery would also summate in elicit-ing a stronger return of fear. The potential additivityof these phenomena is of interest in practical termsbecause it gives us a higher level of recovered fear thatshould be more sensitive to the evaluation of theeffects of different manipulations aimed at reducingthe return of fear. In addition, a situation in which

251prevent ing return of fear

renewal and spontaneous recovery summate may beconsidered more naturalistic, in the sense that relapseafter exposure therapy usually occurs when patientsconfront disorder-related stimuli outside of thetreatment context and after a relatively long timeafter the endof treatment (e.g., Bouton, 1988;Craske,1999; Rachman, 1979, 1989).A second consequence of an associative interference

view of extinction (e.g., Laborda & Miller, 2012;Miller & Laborda, 2011) is that the return ofconditioned fear following extinction (and likely,relapse from exposure therapy) can be attenuated bymanipulations that enhance either the strength of theextinction association (i.e., CS-noUS) or the presenceat test of cues from extinction that facilitate retrievalofmemories fromextinction treatment.Herewe focuson two of thesemanipulations: the use of extinction inmultiple contexts, which arguably promotes general-ization of facilitatory cues from the extinction to thetest context, and the use of a massive number ofextinction trials, which arguably enhances the extinc-tion learning.Gunther, Denniston, and Miller (1998) assessed

whether using multiple extinction contexts wouldhave an effect on the level of return of fearexpressed at test. In their study, rats in a fearconditioning preparation were trained to fear anauditory CS by pairing it with a mild footshock(i.e., US) in Context A. After this training, rats in theexperimental groups received a moderate amountof extinction treatment, either in a single new context(Context B) or in three different new contexts(Context B, C, and D). At test in the associativelyneutral Context E, rats that received extinctiontreatment in multiple contexts were less fearful ofthe CS (i.e., they showed less renewal) than rats thatreceived the same extinction treatment but in a singlecontext. The attenuation of the return of extinguishedresponding by training extinction inmultiple contextshas been replicated and extended in many differentsituations (e.g., Bandarian Balooch & Neumann,2011; Chelonis, Calton, Hart, & Schachtman, 1999;Glautier & Elgueta, 2009; Neumann, 2006; Pineño& Miller, 2004; Thomas, Vurbic, & Novak, 2009;Vansteenwegen et al., 2007; for negative results seeBetancourt et al., 2008; Bouton, García-Gutiérrez,Zilski, & Moody, 2006; Neumann, Lipp, & Cory,2007), and today is a well-documented result.Successful applications of this technique have alsobeen reported in preclinical studies with humans.Neumann (2006) found reduced ABC and ABArenewal after extinction in multiple contexts in aconditioned suppression task, and Vansteenwegen etal. (2007) found that exposing spider-fearful partic-ipants to a spider videotaped in three different roomsof a house attenuated recovery of extinguished fear

when the test occurred in a neutral context (i.e., anABC-like design).Denniston, Chang, and Miller (2003) assessed

whether using a massive number of extinction trialswould have an effect in the level of return of fearexpressed at test. In their study, rats were trained tofear an auditory CS by pairing it with a mildfootshock (i.e., US) in Context A. After this training,rats received either a moderate (160) or a massive(800) number of extinction trials in Context B. Therats were then tested either in a neutral context orback in the acquisition context. Rats that receivedmassive extinction treatment were less fearful to theCS (i.e., they showed less renewal) than rats thatreceived a moderate amount of extinction. Asdiscussed elsewhere (Laborda,McConnell,&Miller,2011), those studies that have failed to find decreasedrecovery of fear with massive extinction trials usedfar fewer extinction trials (e.g., Thomas et al., 2009,used 144 trials; Rauhut, Thomas, & Ayres, 2001,used 100 trials; and Tamai & Nakajima, 2000, used112 trials) than Denniston et al. (800 trials), whichexplains the different results. Of interest, the effect ofmassive exposure has also been found in clinicalsettings. For example, some researchers (Foa et al.,2005; Powers, Halpern, Ferenschak, Gillihan, &Foa, 2010) have observed that prolonged exposurereduces relapse in patients treated for posttraumaticstress disorder. Given that prolonged exposure andmassive extinction both increase the time spent in thepresence of the CS, it is possible that these twomanipulations share the same underlying mecha-nisms (e.g., enhanced CS-noUS learning).Critically, Thomas et al. (2009) found that

extinction in multiple contexts was only effective inreducing ABA renewal when a moderate number ofextinction trials were used (144) in comparison withfew extinction trials (36). Therefore, at least undercertain parameters, the amount of extinction treat-ment seems to interact (instead of summate) with thenumber of contexts in which the extinction treatmenttakes place, which could explain why some re-searchers have failed to find an effect of extinctionin multiple contexts alone (e.g., Bouton et al., 2006).In Thomas et al.'s study, eachmanipulation alonewasineffective in reducing the return of fear when subjectswere tested back in the acquisition context, but theyhad amultiplicative (i.e., interactive) effect when usedtogether.In summary, in the present series of experiments

we evaluated a) whether spontaneous recovery andABC renewal summate provoking an especiallystrong return of fear (Experiment 1), and b) whethertwo effective behavioral techniques for reducingreturn of conditioned fear (i.e., extinction in multiplecontexts and massive extinction) summate to further


prevent the return of fear after a spatiotemporalcontext shift.

Experiment 1: Renewal andSpontaneous Recovery

Experiment 1 was designed to evaluate whether thereturn of fear produced by a mismatch between thecontext of extinction and testing (i.e., renewal)summates with the return of fear produced byinserting a long retention interval between extinctionand testing (i.e., spontaneous recovery) in a fearconditioning preparation (see Table 1 for details). Wehypothesized that if these manipulations summate,then subjects tested after a long delay and outside thecontext of extinction should exhibit stronger recoveryof extinguished fear responses than subjects that aretested with either restorative manipulation alone. Theadditivity of these phenomenawould be evident if in a2 (Time of testing: Short delay v. Long delay)×2(Context of testing: Context of extinction v. Neutralcontext) factorial ANOVAwe find both a main effectof time of testing and of context of testing, in theabsence of an interaction between these factors. Infact, an interaction between them would suggest thatthe effects of our manipulations are multiplicative(i.e., interactive) rather than additive (i.e., summative;seeMyers&Wells, 2003). An interaction of these twomanipulations seemed unlikely because space andtime seemingly constitute independent dimensions.To evaluate the effect of a delay between extinction

and testing (i.e., spontaneous recovery), two controlswere necessary. Groups Ext1 andRen1 controlled forthe time between acquisition and extinction, butconfound the total interval between acquisition andtesting, andGroups Ext2 and Ren2 controlled for thetotal interval between acquisition and testing, butconfound the interval between acquisition andtesting. Collectively Groups Ext1 and Ext2 permitassessment of spontaneous recovery. Groups Ext1and Ext2, likeGroups Ren1 andRen2,were expectedto behave similarly, but that is an empirical question.

Table 1Design Summary of Experiment 1

Groups Acquisition RetentionInterval 1

Acq 8 X+(A) –

ExtExt1 8 X+(A) –Ext2 8 X+(A) 21 Days

RenRen1 8 X+(A) –Ren2 8 X+(A) 21 Days

Sp-Rec 8 X+(A) –Ren+Sp-Rec 8 X+(A) –

Note. CS Xwas a 10-s click train. “+” denotes reinforcement with a brief fooand C, are different contexts. Numbers preceding letter X indicate total nu

methods

SubjectsThe subjects were 42 male (292–430 g) and 42female (213–288 g), experimentally naive, Sprague-Dawley descended rats obtained from our ownbreeding colony. Subjects were randomly assignedto one of seven groups (ns=12; Acq, Ext1, Ext2,Ren1, Ren2, Sp-Rec, and Ren+Sp-Rec, where Acq=Acquisition, Ext=Extinction, Ren=Renewal, andSp-Rec=Spontaneous recovery), counterbalancedwithin groups for sex. The animals were individuallyhoused in standard hanging stainless-steel wire-meshcages in a vivarium maintained on a 16/8-hr light/dark cycle. Experimental manipulations occurredduring the light phase. The animals received freeaccess to Purina Lab Chow, whereas water avail-ability was limited to 20 min per day following aprogressive deprivation schedule initiated 1 weekprior to the start of the study. From the time ofweaning until the start of the study, all animals werehandled for 30 s, three times per week.

ApparatusTwenty-four experimental chambers, of three differ-ent types, were used. Chamber type 1 (Ch1) was30-cm long, 30-cm wide, and 27-cm high. Thesidewalls of the chamber were made of stainless steelsheet metal, and the front wall, back wall, and ceilingof the chamberweremade of clear Plexiglas. The floorwas constructed of 0.3 cm diameter rods, spaced1.3 cm center-to-center, and connected byNE-2 neonbulbs that allowed a 1.0-mA, 0.5-s, constant-currentfootshock to be delivered by means of a high voltageAC circuit in series with a 1.0-MΩ resistor. Each oftwelve copies of Ch1was housed in an environmentalisolation chest that was dimly illuminated by ahouselight (1.12-Watt, #1820 incandescent bulb)mounted high on one wall of the experimentalchamber.Chamber type 2 (Ch2) was rectangular, measuring

24.0×9.0×12.5-cm (l x w x h). The walls and ceiling

Extinction RetentionInterval 2

Test

(B)/(C) – X (C)162 X- (B)/(C) – X (B)162 X- (B)/(C) – X (B)162 X- (B)/(C) – X (C)162 X- (B)/(C) – X (C)162 X- (B)/(C) 21 Days X (B)162 X- (B)/(C) 21 Days X (C)

tshock. “-” denotes no reinforcement. “–” denotes no treatment. A, B,mber of trials in that phase. See text for details.


of Ch2 were clear Plexiglas, and the floor wascomprised of stainless steel rods measuring 0.5-cmdiameter, spaced 1.3-cm apart (center to center). Thefloor of Ch2 could provide footshock identical to thatof Ch1. Each of six copies of Ch2 was housed in aseparate light- and sound-attenuating environmentalisolation chest. Each chamber was dimly illuminatedby a 2-W (nominal at 120 VAC, but driven at 50VAC) incandescent house light mounted on an insidewall of the environmental chest located approximate-ly 30-cm from the center of the animal enclosure.Chamber type 3 (Ch3) was 27-cm long, 29.5-cm

high, 21.5-cmwide at the top, and 5.5-cmwide at thebottom. The floor was comprised of two 27-cm longplates, 2-cm wide, with a 1.5-cm gap between thetwo plates. The ceiling was clear Plexiglas, the frontand back walls were black Plexiglas, and the sidewalls were stainless steel. The floor and side walls ofCh3 could provide footshock identical to that of Ch1and Ch2. Each of six copies of Ch3 was housed in aseparate sound- and light-attenuating environmentalisolation chest. The chamber was illuminated by a7-W (nominal at 120 VAC, but driven at 60 VAC)light bulb, which was mounted on the inside wall ofthe environmental chest, approximately 30-cm fromthe center of the experimental chamber. Lightentered the chamber primarily by reflection fromthe ceiling of the environmental chest.Each instance of Ch2 and Ch3 could be equipped

with awater-filled lick tube that extended1-cm into acylindrical niche, which was 4.5-cm in diameter, leftright centered, with its bottom 1.75-cm above thefloor of the apparatus and 5.0-cm deep. In the samemanner, Ch1 could be equipped with a water-filledlick tube that extended about 1 cm from the rear of aniche (4×4×5.5 cm, l×w×h) placed on the frontwall. The lick tube entered the center of this niche3.3 cm above the niche floor, which was at the levelof the grid floor. In all chambers there was aphotobeam detector 1-cm in front of the lick tubethatwas brokenwhenever the subject licked the tube.A 45-Ω speaker on an inside walls of each isolationchest could deliver a click train (6 Hz, 6 dB on the Cscale above background). Ventilation fans in eachenclosure provided a constant 76-dB backgroundnoise. The light intensities inside the three chamberswere approximately equal due to the difference inopaqueness of the walls.A 10-s click train served as CS X and a 0.5-s

footshock served as US. Context A consisted of aninstance of Ch1 with the house light (HL) off, and ablock of wood with two drops of banana essencelocated inside the isolation chest. Contexts B and Cwere Ch2 and Ch3, counterbalanced in these roleswithin groups. No nominal odor cue was added tothese contexts.

procedure

AcclimationOn Days 1 and 2, all subjects were acclimated toContexts A, B, and C for 30 min. All subjects wereexposed to Context B and C (in that order) on Day 1and to Context A on Day 2. During the acclimationphase subjects did not have access to the water-filledlick tubes. There were no presentations of the CS orUS during this phase.

AcquisitionOn Days 3 and 4, all subjects received 60-minconditioning training sessions in Context A. Subjectsreceived 4 daily presentations of X co-terminatingwith the US with a mean intertrial interval (ITI) of15 min (from CS onset to CS onset). The reinforcedtrials occurred at 5, 16, 36, and 52 min into thesession.

Retention Interval 1BetweenDays 5 and 25, subjects of Groups Ext2 andRen2 stayed in their home cages and no furthertraining took place. During this period, subjects werehandled for 30 sec, three times per week.

ExtinctionAll groups, except Group Acq, received 162 extinc-tion trials in Context B and equal amount ofexposure to Context C. Group Acq simply receivedequal exposure to both contexts. All sessions were2.25 hr in duration. The long duration of thesesessions was unnecessary in Experiment 1, but wasused to maintain similarity of parameters withExperiment 2. For all groups receiving extinctiontreatment, trials occurredwith amean ITI of 30 s (CSonset to CS onset; range=15-45 s). The extinctiontrials were delivered in a block at the beginning or atthe end of the extinction session, counterbalancedwithin groups. For Groups Ext1, Ren1, Sp-Rec, andRen+Sp-Rec, the extinction sessions consisted ofnon-reinforced presentations of X in Context B onDays 6, 8, and 10, and context exposure sessionsconsisted of exposure to Context C without pre-sentations of X on Days 5, 7, and 9. Group Acq wasexposed to Context B and C on the same schedule.For Groups Ext2 and Ren2 the extinction sessionsconsisted of nonreinforced presentations of X inContext B on Days 27, 29, and 31, and contextexposure sessions consisted of exposure toContextCwithout presentations of X on Days 26, 28, and 30.

Retention Interval 2Between Days 11 and 31, subjects of GroupsSp-Rec and Ren+Sp-Rec stayed in their homecages and no further treatment took place. Subjectswere handled for 30 sec, three times per week.

FIGURE 1 Results of Experiment 1. Mean log10 time tocomplete 5 cumulative seconds of licking in the presence oftarget CS (X). Brackets represent the standard error of the means.Higher scores indicate more conditioned fear. Acq=group thatreceived no extinction trials and was tested in a neutral but familiarcontext (C); Ext=group that received a moderate number ofextinction trials in only one context (B) and was tested in theextinction context following a short delay after extinction; Ren=group that received a moderate number of extinction trials in onlyone context (B) and was tested in a neutral but familiar context (C)after a short delay following extinction; Sp-Rec=group thatreceived a moderate number of extinction trials in only onecontext (B) and was tested in the extinction context after a longdelay following extinction; Ren+Sp-Rec=group that received amoderate number of extinction trials in only one context (B) andwas tested in a neutral but familiar context (C) after a long delayfollowing extinction. See text and Table 1 for further details.


ReacclimationAll subjects were reacclimated to Contexts B and Cin two daily 30-min sessions (with the order ofexposure to the contexts counterbalanced withingroups). In these sessions subjects had free access tothe water-filled lick tubes, and no nominal stimuliwere programmed to occur. The purpose of thesesessions was to establish a stable rate of drinkingbehavior, thereby providing similar baseline behav-ior across groups upon which conditioned licksuppression could be assessed. For Groups Ext1,Ren1, and Acq, the reacclimation sessions occurredon Days 11 and 12. For Groups Ext2, Ren2,Sp-Rec, and Ren+Sp-Rec, these sessions occurredon Days 32 and 33.

TestingAll subjects were tested for conditioned licksuppression to the target cue X on the day afterreacclimation was completed. Upon placement inthe test chamber, time spent drinking by eachsubject was recorded. Immediately after completionof an initial 5 cumulative seconds of licking in theabsence of any nominal stimulus, subjects werepresented with CS X (i.e., the click train) for15 min. Thus, all subjects were drinking at the timeof CS onset. Time to complete an additional 5cumulative seconds of licking in the presence of Xwas recorded. The times recorded during thepresentation of X were interpreted as reflectingsubjects’ expectancy of the US following onset of X.The test session was 16 min in duration, and aceiling score of 15 min was imposed on the time tocomplete 5 cumulative seconds of drinking in thepresence of X. In practice, only one rat (fromGroupAcq) reached the 15 min ceiling score. Followingthe convention of our laboratory, all animals thattook more than 60 s to complete their first 5cumulative seconds of licking (i.e., prior to CSonset) during the test session were scheduled to beeliminated from the study because such longlatencies may be considered indicative of unusuallygreat fear of the test context. In practice, one subjectfrom Group Sp-Rec met this elimination criterionand was excluded from all analyses.Consistent with the experimental design, some

groups were tested in a test session on Day 13and others in a test session on Day 34. Duringthe Day 13 test session, subjects from GroupsRen1 and Acq were tested in Context C, whilesubjects from Group Ext1 were tested in ContextB. During the Day 34 test session, subjects fromGroups Ext2 and Sp-Rec were tested in ContextB, while subjects from Groups Ren2 and Ren+Sp-Rec were tested in the same manner but inContext C.

Data AnalysisLatencies to drink for 5 cumulative seconds beforethe onset of the test stimulus (i.e., pre-CS measure)and after the onset of the test stimulus (i.e., CSmeasure) were transformed to log10 to betterapproximate the normal distributions assumed byparametric statistical analyses. Analyses of variance(ANOVA) were used to evaluate potential baselinedifferences and to determine whether our manipula-tions affected subjects’ log latencies to drink in thepresence of the test stimulus. The error term from theANOVA served as an estimate of within-groupvariance in planned comparisons. Effect size wasestimated using Cohen's f (Myers & Wells, 2003).Alpha was set at .05.

results and discussion

As can be seen in Figure 1, in the present study wefound acquisition, extinction, ABC renewal, sponta-neous recovery, and more important, we found thatABC renewal and spontaneous recovery summatedproducing significantly more return of fear thanrenewal, but only numerically more return of fearthan spontaneous recovery. The following statisticalanalysis supported these conclusions.A one-way ANOVA applied to the log pre-CS test

data showednodifferences among groups in baselinedrinking behavior, F(6, 76)=1.76, p=0.12, MSE=


0.04, indicating that the experimental groups did notappreciably differ in their baseline behavior. How-ever, the same analysis proved to be significant whenthe log CS data were examined, F(6, 76)=8.31,pb .001,MSE=0.17, Cohen's f =0.73. Four plannedcomparisons were then performed. A significantdifference was found when Group Acq was com-pared with Groups Ext1, F(1, 76)=29.58, pb .001,and Ext2, F(1, 76)=30.67, pb .001, indicating thatthe extinction treatment used was successful inreducing fear responding in our preparation. Thelevel of conditioned responding after extinctiontreatment did not differ between Groups Ext1 andExt2, F(1, 76)=0.01, p=0.92, indicating that a delaybetween acquisition and extinction had negligibleimpact on the consequences of the extinctiontreatment. The similar level of responding betweenGroups Ext1 and Ext2 was confirmed by a Bayesiananalysis with odds of 16.68 in favor of the nullhypothesis (Rouder et al., 2009). Considering theseresults, Groups Ext1 and Ext2were pooled as GroupExt for all further statistical analyses. A similarsituation occurred with Groups Ren1 and Ren2. Thelevel of responding did not differ between GroupsRen1 and Ren2, F(1, 76)=0.01, p=0.94, alsoindicating that a delay between acquisition andextinction had negligible impact on the consequencesof the extinction treatment. The similar level ofresponding between Groups Ren1 and Ren2 wasconfirmed by a Bayesian analysis with odds of 16.78in favor of the null hypothesis (Rouder et al.).Considering these results, Groups Ren1 and Ren2were pooled as Group Ren for all further statisticalanalyses.The additivity of ABC renewal and spontaneous

recovery was tested with a 2 (Time of testing: Shortdelay vs. Long delay)×2 (Context of testing: B vs. C)factorial ANOVA. This analysis showed a maineffects of the time of testing, F(1, 67)=17.75,pb .001, MSE=0.15, Cohen's f =0.49, indicatingthat more return of fear occurredwhen subjects weretested after a long delay following extinction thanwhen they were tested after a short delay followingextinction (i.e., spontaneous recovery was observed).The main effect of the context of testing was alsosignificant, F(1, 67)=9.29, pb .001, Cohen's f =0.34, indicating that more return of fear occurredwhen subjects were tested outside the context ofextinction than when subjects were tested in thecontext of extinction (i.e., ABC renewal wasobserved). Of importance, the interaction betweenthese factors did not prove significant, F(1, 67)=0.27, p=.60, suggesting that these effects summatedinstead of interacted to produce more return of fear.Two planned comparisons were then performed. Asignificant difference was found when Group Ren

was compared with Group Ren+Sp-Rec, F(1, 67)=7.04, pb .001, confirming that the return of fear wassignificantly stronger following a spatiotemporalcontext shift than following a spatial context shiftalone. A similar analysis showed that Group Sp-Recdid not significantly differ fromGroup Ren+Sp-Rec,F(1, 67)=2.37, p=0.13, although the numericaldifference was in the expected direction (i.e.,Sp-RecbRen+Sp-Rec).In summary, the present results showed return of

fear when testing occurred in a neutral but familiarcontext andwhen a long delay was imposed betweenextinction treatment and testing. Importantly, thesemanipulations summated to produce a strongerreturn of fear than did either of themused separately;the combined effect was significantly stronger thanrenewal alone, but only numerically stronger thanspontaneous recovery alone. This result is notsurprising, but neither it is obvious, as the twomanipulations could have been exploiting a commonsource that might have been exhausted by eithermanipulation alone. The extremely effective returnof fear observed with combined ABC renewal andspontaneous recovery provided a high baseline toinvestigate potential means of preventing the returnof fear in Experiment 2 (also see, Laborda, Miguez,& Miller, 2012).

Experiment 2: Massive Extinction in MultipleContexts

Experiment 2 was designed to evaluate the conjointeffects of extinction in multiple contexts (Gunther etal., 1998) and massive extinction (Denniston et al.,2003) in a situation in which renewal and spontane-ous recovery summate. Thomas et al. (2009) recentlyassessed the conjoint effect of these manipulations inan ABA renewal situation, finding reduced return offear only when both manipulations were usedtogether, with each manipulation alone not beenmore effective than a control group that received a fewextinction trials in only one context. No summativeeffect was detected; instead, two underpoweredmanipulations were found to have a multiplicativeeffect making their collective effects significant.There are several differences between Thomas et al.

(2009) and the present study, but most important:(a) we used parameters that have proven to beeffective in reducing the return of fear with extinctionin multiple context alone (Gunther et al., 1998);(b) we used parameters that have proven to be effec-tive in reducing the return of fear with massive ex-tinction treatment alone (Denniston et al., 2003);(c) and we evaluated the summative effect of thesemanipulation in reducing a stronger return of fearprovoked by a delayed context shift. Critically,Thomas et al. confounded the increase in extinction


trials with an increase in the number of extinctionsessions, which by itself may have reduced the returnof fear as extinguishing inmultiple sequential sessionscan be considered extinction in multiple temporalcontexts (for a similar analysis of the role of sessionsin the return of fear, see Laborda, Miguez, &Miller,2012). Here we controlled for this confounding bykeeping the number and length of the extinctionsessions constant while manipulating only the num-ber of extinction trials.We hypothesized that extinction treatment in

multiple contexts andmassive amounts of extinctiontreatment would reduce the strong return of fear seenin Experiment 1 (i.e., Group Ren+Sp-Rec). More-over, we hypothesized that both of these manipula-tions applied together would be more effective inattenuating the return of fear than eachmanipulationalone (see Table 2 for details). Massive extinctionwas expected to strengthen thememory of extinctiontreatment, whereas extinction in multiple contextswas expected to encourage the generalization offacilitatory cues from the extinction context(s) tothe test context. As these two mechanisms appear tobe independent (e.g., Miller & Laborda, 2011),summation of these twomanipulationswas expectedrather than an interaction. The additivity of thesetechniques would be evident if in a 2 (Extinctioncontexts: Single v. Multiple)×2 (Extinction trials:Moderate v. Massive) factorial ANOVA we foundsignificantmain effects of these factors in the absenceof an interaction between them. In fact, an interac-tion between them would suggest that the effects ofour manipulations are multiplicative (or interactive)rather than additive (or summative) (see Myers &Wells, 2003).

method

SubjectsSubjects were 24 male (167 – 272 g) and 24 female(166 – 221 g), experimentally naive, Sprague-Dawley

Table 2Design Summary of Experiment 2

Groups Acquisition Extinction

Single/Moderate

8 X+(A) 162 X- (B) (C)

Single/Massive

8 X+(A) 810 X- (B) (C)

Multiple/Moderate

8 X+(A) 54 X- (B) 54 X- (C)

Multiple/Massive

8 X+(A) 270 X- (B) 270 X- (C

Note. CS X was a 10-s click train. “+” denotes reinforcement with a bridifferent contexts. Numbers preceding letter X indicate total number of

descended rats obtained from our own breedingcolony. Subjects were randomly assigned to one offour groups (ns =12; Single/Moderate, Single/Massive, Multiple/Moderate, andMultiple/Massive,where Single=single extinction context, Multiple=multiple extinction contexts, Moderate=moderatenumber of extinction trials, and Massive=massivenumber of extinction trials), counterbalanced withingroups for sex. The maintenance and housing ofsubjects were the same as in Experiment 1.

ApparatusThe chambers and stimuli used in Experiment 2were the same as those used in Experiment 1 exceptwhere otherwise described. Six additional Ch2 wereused. Five physical contexts were used in this study,one for conditioning (Context A), three forextinction (Contexts B, C, and D), and one fortesting (Context E). Context A consisted of aninstance of Ch1 with the house light (HL) off, and ablock of wood with two drops of banana essencelocated inside the isolation chest. No Plexiglas floorwas used in this context. The physical contexts usedas Contexts B, C, and D were counterbalancedwithin groups. The three extinction contexts were:(1) an instance of Ch2 with HL off, a block of woodwith two drops of 98% methyl salicylate, andPlexiglas floor; (2) an instance of Ch2 (differentfrom the one used as [1]) with HL on (no Plexiglasfloor or odor cue was used in this context); (3) aninstance of Ch3 with the HL on. Finally, Context Econsisted of an instance of Ch1 (different from theone used as Context A) with HL on and a Plexiglasfloor. No odor cue was used in this context.

procedure

AcclimationOn Day 1, all subjects were acclimated to theirversions of Context E for 30 min. Subjects wereacclimated only to Context E because that is where

RetentionInterval

Test

(D) (E) 21 Days X (E)

(D) (E) 21 Days X (E)

54 X- (D) (E) 21 Days X (E)

) 270 X- (D) (E) 21 Days X (E)

ef footshock. “-” denotes no reinforcement. A, B, C, D, and E aretrials in that phase. See text for details.


all animals were tested. During the acclimationphase, subjects had access to water-filled lick tubes.As in Experiment 1, there were no presentations ofthe CS or US during this phase.

AcquisitionOn Days 2 and 3, all subjects received 60-minconditioning training sessions in Context A, exactlyas described in Experiment 1.

ExtinctionDuring this phase of the experiment, all subjectsreceived an equal amount of exposure to Contexts B,C, D, and E in accordance with the experimentaldesign (see Table 3, which summarizes the order ofsessions, the amount of extinction, and the context ofextinction for all groups). During these sessions,subjects in Condition Single received extinction trialsin Context B and equal exposure to Contexts C, D,and E. Subjects in Condition Multiple receivedextinction trials in Contexts B, C, and D and equalexposure toContext E. ConditionModerate receivedmoderate extinction treatment (162 trials), whereasCondition Massive received massive amount ofextinction treatment (810 trials). Extinction sessionsconsisted of nonreinforced presentations of X in theappropriated context (Days 7, 11, and 15). Contextexposure sessions consisted of exposure to theappropriated context without presentations of X toequally expose subject to Context B, C, D, and E(Days 4-6, 8-10, and 12-14). Lick tubes were presentonly during exposure to Context E, which servedlater as the test context for all groups. All sessionswere 2.25 hr in duration. For all groups, extinctiontrials had a mean ITI of 30 s (CS onset to CS onset;range=15–45 s). To accomplish this, while avoidingconfounding session duration and trial spacing,groups that received 54 extinction trials per sessionreceived them in a block at the middle of theextinction session.

Table 3Order of Extinction and Context Exposure Sessions in Experiment

Days4, 5, 6

Day7

Days8, 9, 10

Single/Moderate

(E), (D), (C) 54 X- (B) (E), (D),

Single/Massive

(E), (D), (C) 270 X- (B) (E), (D),

Multiple/Moderate

(E), (D), (C) 54 X- (B) (E), (D),

Multiple/Massive

(E), (D), (C) 270 X- (B) (E), (D),

Note. Following the experimental design, each group received a numbeDuring the rest of the days (Days 4-6, 8-10, and 12-14), exposure to Coextinction session. See text for details.

Retention IntervalBetween Days 16 and 36, all subjects stayed in theirhome cages and no treatment took place. Subjectswere handled for 30 s, three times per week.

ReacclimationOnDays 37 and 38, all subjects were reacclimated intwo daily 30-min sessions to Contexts E. The rest ofthe procedure was identical to that of Experiment 1.

TestingOnDay 39, all subjects were tested one at a time forconditioned lick suppression to X in Context E. Therest of the testing procedures were the same as inExperiment 1. In the present experiment no subjectsmet the exclusion criteria (i.e., more than 60 s tocomplete their first 5 cumulative seconds of lickingprior to CS onset) and no subjects reached theceiling of 15 min during testing.

Data AnalysisAs in Experiment 1, latencies to drink for fivecumulative seconds before the onset of the teststimulus (i.e., pre-CS measure) and after the onset ofthe test stimulus (i.e., CS measure) were transformedto log10 to better approximate the normal distribu-tions assumed by parametric statistical analyses.Analyses of variance (ANOVA)were used to evaluatepotential baseline differences and to determinewhether our manipulations affected subjects’ loglatencies to drink in the presence of the test stimulus.The error term from the ANOVA served as anestimate of within-group variance in planned com-parisons. Effect size was estimated using Cohen's f(Myers & Wells, 2003). Alpha was set at .05.

results and discussion

The results of Experiment 2 are depicted in Figure 2.In this experiment strong return of fear wasexpected in all subjects (i.e., they were trained in a

2

Day11

Days12, 13, 14

Day15

(C) 54 X- (B) (E), (D), (C) 54 X- (B)

(C) 270 X- (B) (E), (D), (C) 270 X- (B)

(B) 54 X- (C) (E), (B), (C) 54 X- (D)

(B) 270 X- (C) (E), (B), (C) 270 X- (D)

r of extinction trials in the indicated context on Days 7, 11, and 15.ntexts B, C, D, and E was equated for each group over the entire

FIGURE 2 Results of Experiment 2. Mean log10 time tocomplete 5 cumulative seconds of licking in the presence of thetarget CS (X) after a long delay following extinction in a neutral butfamiliar context (E) for all groups. Brackets represent the standarderror of the means. Higher scores indicate more conditioned fear.Single=condition that received extinction trials in only onecontext (B); Multiple=condition that received extinction trials inthree different contexts (B, C, and D); Moderate=condition thatreceived a moderate number of extinction trials (162); Massive=condition that received a massive number of extinction trials (810).See text and Tables 2 and 3 for further details.


design that allows ABC renewal and spontaneousrecovery to summate, see Experiment 1); however,in three of the four groups we observed someattenuation of this reappearance of fear. As predicted,Group Single/Moderate exhibited the strongest re-turn of fear at test (highly similar in degree to therecovery of fear observed in the similarly treatedGroup Ren+Sp-Rec of Experiment 1, but thisassessment should be taken with caution given itrelies on a cross-experiment comparison). Thisreturn of fear was attenuated when extinctiontook place in multiple contexts (Group Multiple/Moderate) and when massive extinction treatmentwas administered (Group Single/Massive). Impor-tantly, when both behavioral manipulations wereused together, return of fear was weaker than wheneach manipulation was used alone. Moreover, itseems that the joint effect of our manipulationstotally abolished the return of fear, as is suggested byrats in Group Massive/Multiple exhibiting even lesssuppression than the Group Ext in Experiment 1(however, as a cross-experiment comparison, thisclaim should be taken with caution). The followingstatistical analysis supported these conclusions.A 2 (Contexts of extinction: Single vs.Multiple)×2

(Number of extinction trials: Moderate vs. Massive)ANOVA applied to the log pre-CS on the test datashowed a nonsignificant main effect of number ofextinction contexts, F(1, 44)=0.04, p=.85, MSE=0.06, a nonsignificant main effect of number ofextinction trials, F(1, 44)=0.05, p= .83, and anonsignificant interaction of these factors, F(1, 44)=

1.77, p=.19, indicating that the experimental groupsdid not significantly differ in baseline drinkingbehavior. A similar analysis was performed toevaluate the additivity of massive extinction andextinction in multiple contexts. This analysis onconditioned suppression during the CS (i.e., log CSdata) revealed a significant main effects of number ofextinction contexts, F(1, 44)=17.23, pb .001,MSE=0.19, Cohen's f =0.58, indicating that extinction inmultiple context decreased the return of fear. Themain effect of number of extinction trials was alsosignificant, F(1, 44)=15.04, pb .001, Cohen's f =0.54, indicating that massive extinction trials reducedthe return of fear. Of central importance, theinteraction between these factors did not provesignificant, F(1, 44)=2.04, p=.16, suggesting thatthese effects primarily summated instead of interactedto reduce the return of fear. Two planned compar-isons were then performed. A significant differencewas found when Group Single/Massive was com-pared with Group Multiple/Massive, F(1, 44)=15.60, pb .001, indicating that the return of fearwas weaker following massive extinction in multiplecontexts than following massive extinction alone. Asignificant difference was also found when GroupMultiple/Moderate was compared with GroupMultiple/Massive, F(1, 44)=14.07, pb .001, indicat-ing that the return of fear was weaker followingmassive extinction in multiple contexts than follow-ing extinction in multiple contexts alone.In summary, the present results showed that

massive extinction treatment and extinction inmultiple contexts were effective in reducing thereturn fear produced by a spatiotemporal contextshift. Moreover, both techniques together furtherreduced this strong return of fear. Analogous to thesummation effect seen in Experiment 1, the opposingsummation effect observed in Experiment 2 is notsurprising; however, it is not foreordained, as one ofthe manipulations to prevent the return of fear couldhave rendered the other ineffectual.

General DiscussionIn Experiment 1, subjects that were tested after aspatiotemporal context shift displayed more returnof fear than subjects that were tested after a physicalor temporal context shift alone. In other words, ABCrenewal and spontaneous recovery summated, pro-ducing a stronger return of fear. However, thestronger return of fear evidenced with conjointrenewal and spontaneous recovery was only numer-ical when compared to spontaneous recovery alone.These results extend Rosas and Bouton's (1998)findings to a fear conditioning preparation. Forresearch purposes, a preparation that producesstrong return of fear is especially useful because it

image of Figure�2


should be highly sensitive to techniques designed toreduce fear reappearance. Also, a preparation thatencourages return of fear through spatiotemporalchanges seems to be more naturalistic than othersituations, given that relapse fromexposure therapiesis most common when patients confront disorder-related stimuli outside the psychotherapeutic clinicand after an interval following the end of treatment(e.g., Craske, 1999; Rachman, 1989).In Experiment 2, subjects that received massive

extinction treatment in multiple contexts displayedless return of fear than subjects that received massiveextinction treatment alone or extinction treatment inmultiple contexts alone. Each of these techniquesalone was effective in reducing the return of fear aftera spatiotemporal context shift (extending Gunther etal.'s 1998 and Denniston et al.'s 2003 findings to adifferent preparation); moreover, both techniquestogether were highly effective in reducing this strongreturn of fear.In previous research, Thomas et al. (2009) found

an interactive (insteadof a summative) effect betweenextinction in multiple contexts and massive extinc-tion training. The difference with the present resultsis likely due to two factors. First, each manipulationin Thomas et al.'s study was by itself ineffective inreducing the return of fear. It may be true that theimplementation of underpowered versions of thesetechniques together interact and reach a threshold toaffect behavior. In our study, each technique by itselfwas effective in reducing the return of fear, whichseemed to encourage a summation of their individualeffects. Second, in Thomas et al.'s study moreextinction trials were confounded with more extinc-tion sessions. Given that each successive extinctionsession may enhance the generalization of extinctionlearning to different temporal test contexts (for ananalysis of time as context, see Bouton, 2010; also seeLaborda, Miguez, & Miller, 2012), their resultsshould be considered with caution.It is worth noting that an interference account of

extinction (e.g., Laborda & Miller, 2012; Miller &Laborda, 2011) predicts all of the results presentedhere. In the case of the present study, the amount ofcontextual change between the context of extinctionand the context of testing was expected to bepositively correlated with the amount of return offear at test, as was observed in Experiment 1. Also,according to this account, techniques that enhanceextinction learning (such as administering a verylarge amount of extinction treatment) and techniquesthat augment the potential facilitatory cues from thecontext of extinction that are present at test (such asextinguishing in multiple contexts) are expected tosummate in reducing the return of fear, as wasobserved in Experiment 2.

An important constraint for the translation of thepresent results to clinical situations comes from theresults of Gunther et al.'s (1998) Experiment 2. Thebenefit of extinguishing in multiple contexts disap-peared when acquisition was also conducted inmultiple contexts. An unfortunate consequence oftheir results is that patients who have experiencedmultiple traumas (e.g., war combatants) or patientswho have used drugs in many situations (e.g.,smokers) may not benefit from this technique alone.However, whether such constraint is eliminatedwhenusingmassive extinction inmultiple contexts is still anexperimental question.In future research some limitations of the present

studies should be considered. First, in Experiment 1the summative effects of ABC renewal and sponta-neous recoverywas documented based on the findingof both effects being significant in the absence of asignificant interaction between them. Then, aplanned comparison confirmed that both manipula-tions used together evoked more return of fear thanonly a physical context shift. However, a secondplanned comparison failed to confirm that bothmanipulations used together evoked more return offear than only a long delay between extinction andtesting (p=.13), although the difference in respond-ing was in the expected direction. Future researchinterested in the relationships between differentsources of return of fear should use longer delaysbetween extinction and testing toward inducingmore spontaneous recovery of fear so that there willbe more return of fear to potentially be countered.Second, our results of Experiment 2 are mute withrespect to the effect of our manipulations onextinction itself, as we did not include ABB controlgroups. Future research should include such groups toevaluate whether our manipulations have an effect inbehavior during extinction (which might well reflectboth associative and nonassociative processes;Rescorla, 2001), or they are just techniques thatenhance generalization to contexts different from thecontext of extinction.Future efforts should also (a) evaluate whether

these techniques can reduce other sources of return offear (e.g., reinstatement and rapid reacquisition),(b) evaluate whether these techniques can reduce thereturn of extinguished responses in other prepara-tions (e.g., alcohol tolerance), and importantly,(c) investigate ways to implement these findings inmore clinical situations. Exposure sessions usingmany fear-eliciting cue exposures in multiple settingsare likely to reduce the return of fear after therapy,but they are apt to require more time and effort onthe part of the therapist.The implementation of the techniques studied here

must be done considering some specific constrains.


The implementation of the multiple contexts manip-ulations in clinical settings may seem easy inprinciple, but clinicians should bear in mind that a“context” is created by a multitude of features ofdifferent dimensions. For example, a context can beinfluenced by the physical background, drug states,mood states, hormonal states, and even by thepassage of time (Bouton, 2010). To put thismanipulation into therapeutic practice, we wouldsuggest planning therapeutic sessions in differentrooms and buildings, with different settings, odors,luminescence, at different times of the day and indifferent days of the week, maybe even with differenttherapists. Implementation of the massive exposurecan take different forms. The problem here is what isconsidered a “trial” in a therapeutic setting. Does anexposure trial consist of every time a patient thinksabout the feared stimulus or only direct exposure tothe feared stimulus? Depending on the conceptual-ization of what is an exposure trial, differentapplications of massive exposure are possible. Also,other factors should be taken into account, such asthe spacing between exposure trials (e.g., Laborda,Miguez, & Miller, 2012; Urcelay, Wheeler, &Miller, 2009).As a final remark, we think that more effort should

be directed toward identifying and evaluating tech-niques to reduce the return of fear in highly controlledanalogue animal models (such as in the presentreport) and in translational studies (such as reportedby Collins & Brandon, 2002, and Rodriguez et al.,1999) because these are the types of studies that couldgive us tools to reduce relapse in clinical settings.Importantly, the summation of techniques to reducethe return of fear, such as the one presented inExperiment 2 and in other reports (e.g., Laborda,Miguez, & Miller, 2012), is a promising result thatmay lead the way to the development of enhancedextinction procedures. Grounding procedures onsolid laboratory research could greatly increase theefficacy of exposure therapy.

References

Bandarian Balooch, S., & Neumann, D. L. (2011). Effect ofmultiple contexts and context similarity on the renewal ofextinguished conditioned behaviour in an ABA design withhumans. Learning and Motivation, 42, 53–63.

Betancourt, R., Corada, L., Dominichetti, J., Laborda, M. A.,Martínez, G., & Miguez, G. (2008). Efecto de la extinciónen múltiples contextos sobre la renovación de la tolerancia alas drogas. Psicothema, 20, 279–283.

Bouton,M. E. (1993). Context, time, andmemory retrieval in theinterference paradigm of Pavlovian learning. PsychologicalBulletin, 114, 80–99.

Bouton, M. E. (1988). Context and ambiguity in the extinctionof emotional learning: Implications for exposure therapy.Behaviour Research and Therapy, 26, 137–149.

Bouton, M. E. (2000). A learning theory perspective on lapse,relapse, and the maintenance of behavior change. HealthPsychology, 19, 57–63.

Bouton,M. E. (2010). Themultiple forms of context in associativelearning theory. InB.Mesquita, L. FeldmanBarrett,&E. Smith(Eds.), The mind in context (pp. 233–258). New York, NY:The Guilford Press.

Bouton, M. E., & Bolles, R. C. (1979). Contextual control ofthe extinction of conditioned fear. Learning andMotivation,10, 445–466.

Bouton, M. E., García-Gutiérrez, A., Zilski, J., &Moody, E. W.(2006). Extinction in multiple contexts does not necessarilymake extinction less vulnerable to relapse. BehaviourResearch and Therapy, 44, 983–994.

Bouton, M. E., & King, D. A. (1983). Contextual control of theextinction of conditioned fear: Tests for the associative valueof the context. Journal of Experimental Psychology: AnimalBehavior Processes, 9, 248–265.

Bouton, M. E., Mineka, S., & Barlow, D. H. (2001). A modernlearning theory perspective on the etiology of panic disorder.Psychological Review, 108, 4–32.

Bouton, M. E., & Nelson, J. B. (1998). The role of context inclassical conditioning: Some implications for cognitive behaviortherapy. In W. O'Donohue (Ed.), Learning and behaviortherapy (pp. 59–84). Boston: Allyn and Bacon.

Chambless, D. L., &Ollendick, T. (2001). Empirically supportedpsychological interventions: Controversies and evidence.Annual Review of Psychology, 52, 685–716.

Chelonis, J. J., Calton, J. L., Hart, J. A., & Schachtman, T. R.(1999). Attenuation of the renewal effect by extinction inmultiple contexts. Learning and Motivation, 30, 1–14.

Collins, B. N., & Brandon, T. H. (2002). Effects of extinctioncontext and retrieval cues on alcohol cue reactivity amongnonalcoholic drinkers. Journal of Consulting and ClinicalPsychology, 70, 390–397.

Craske,M.G. (1999).Anxiety disorders: Psychological approachesto theory and treatment. Boulder, CO: Westview Press.

Craske, M. G., Kircanski, K., Zelikowsky, M., Mystkowski, J.,Chowdhury, N., & Baker, A. (2008). Optimizing inhibitorylearning during exposure therapy. Behaviour Research andTherapy, 46, 5–27.

Craske, M. G., Liao, B., Brown, L., & Vervliet, B. (2012). Roleof inhibition in exposure therapy. Journal of ExperimentalPsychopathology, 3, 322–345.

Denniston, J. C., Chang, R. C., &Miller, R. R. (2003). Massiveextinction attenuates the renewal effect. Learning andMotivation, 34, 68–86.

Effting, M., & Kindt, M. (2007). Contextual control of humanfear associations in a renewal paradigm. Behaviour Researchand Therapy, 45, 2002–2018.

Field, A. P. (2006). Is conditioning a useful framework forunderstanding the development and treatment of phobias?Clinical Psychology Review, 26, 857–875.

Foa, E. B., Hembree, E. A., Cahill, S. P., Rauch, S. A. M., Riggs,D. S., Feeny, N. C., & Yadin, E. (2005). Randomized trial ofprolonged exposure for posttraumatic stress disorder withand without cognitive restructuring: Outcome at academicand community clinics. Journal of Consulting and ClinicalPsychology, 73, 953–964.

Glautier, S., & Elgueta, T. (2009). Multiple cue extinction effecton recovery of responding in causal judgments. InternationalJournal of Comparative Psychology, 22, 254–270.

Gunther, L. M., Denniston, J. C., & Miller, R. R. (1998).Conducting exposure treatment in multiple contexts canprevent relapse.Behaviour Research and Therapy, 36, 75–91.

Laborda, M. A., McConnell, B. L., & Miller, R. R. (2011).Behavioral techniques to reduce relapse after exposure


therapy: Applications of studies of experimental extinction. InT. R. Schachtman & S. Reilly (Eds.), Associative learning andconditioning theory: Human and non-human applications(pp. 79–103). New York, NY: Oxford University Press.

Laborda, M. A., Miguez, G., & Miller, R. R. (2012). Preventingreturn of fear in an animal model of anxiety: Additive effect ofspacing extinction trials and sessions. Manuscript submittedfor publication.

Laborda, M. A., Miguez, G., Polack, C. W., & Miller, R. R.(2012). Animal models of psychopathology: Historicalmodels and the Pavlovian contribution. Terapia Psicológica,40, 45–59.

Laborda, M. A., & Miller, R. R. (2011). S–R associations, theirextinction, and recovery: A new associative account ofphobias without recall of original trauma. Behavior Therapy,42, 153–169.

Laborda, M. A., & Miller, R. R. (2012). Reactivated outcomememories compete for expression after Pavlovian extinction.Behavioural Processes, 90, 20–27.

Laborda, M. A., Witnauer, J. E., & Miller, R. R. (2011).Contrasting AAC and ABC renewal: The role of contextsassociations. Learning & Behavior, 39, 46–56.

McConnell, B. L., &Miller, R. R. (2012). Associative theories ofextinction and recovery-from-extinction effects. Manuscriptsubmitted for publication.

Milad, M. R., Orr, S. P., Pitman, R. K., & Rauch, S. L. (2005).Context modulation of memory for fear extinction inhumans. Psychophysiology, 42, 456–464.

Miller, R.R.,&Laborda,M.A. (2011). Preventing recovery fromextinction and relapse: A product of current retrieval cues andmemory strengths. Current Directions in PsychologicalScience, 20, 325–329.

Mineka, S., & Oehlberg, K. (2008). The relevance of recentdevelopments in classical conditioning to understandingthe etiology and maintenance of anxiety disorders. ActaPsychologica, 127, 567–580.

Myers, J. M., & Wells, A. D. (2003). Research design andstatistical analysis (2nd ed). Mahwah, NJ: Erlbaum.

Neumann, D. L. (2006). The effects of physical context changesand multiple extinction contexts on two forms of renewal ina conditioned suppression task with humans. Learning andMotivation, 37, 149–175.

Neumann, D. L., & Kitlertsirivatana, E. (2010). Exposure to anovel context after extinction causes a renewal of extinguishedconditioned responses: Implications for the treatment of fear.Behaviour Research and Therapy, 48, 565–570.

Neumann, D. L., Lipp, O. V., & Cory, S. E. (2007). Conductingextinction in multiple contexts does not necessarily attenu-ate the renewal of shock expectancy in a fear-conditioningprocedure with humans. Behaviour Research and Therapy,45, 385–394.

Pavlov, I. P. (1927). Conditioned reflexes (G.V. Anrep, Ed. &Trans.). London: Oxford University Press.

Pineño, O., & Miller, R. R. (2004). Signaling a change incue-outcome relations in human associative learning. Learning& Behavior, 32, 360–375.

Powers,M. B.,Halpern, J.M., Ferenschak,M. P., Gillihan, S. J.,&Foa, E. B. (2010). A meta-analytic review of prolongedexposure for posttraumatic stress disorder.Clinical PsychologyReview, 30, 635–641.

Rachman, S. (1979). The return of fear. Behaviour Researchand Therapy, 17, 164–166.

Rachman, S. (1989). The return of fear: Review and prospect.Clinical Psychology Review, 9, 147–168.

Rauhut, A. S., Thomas, B. L., & Ayres, J. J. B. (2001).Treatments that weaken Pavlovian conditioned fear andthwart its renewal in rats: Implications for treating humanphobias. Journal of Experimental Psychology: AnimalBehavior Processes, 27, 99–114.

Rescorla, R. A. (2001). Experimental extinction. In R. R.Mowrer & S.B. Klein (Eds.), Handbook of contemporarylearning theories (pp. 119–154). Hillsdale, NJ: Erlbaum.

Rescorla, R. A., &Wagner, A. R. (1972). A theory of Pavlovianconditioning: Variations in the effectiveness of reinforce-ment and non-reinforcement. In A. H. Black & W.F.Prokasy (Eds.), Classical conditioning II: Current theoryand research (pp. 64–99). New York: Appleton-CenturyCrofts.

Rodriguez, B. I., Craske,M. G.,Mineka, S., &Hladek, D. (1999).Context-specific of relapse: Effects of therapist and environ-mental context on return of fear. Behaviour Research andTherapy, 37, 845–862.

Rosas, J. M., & Bouton, M. E. (1998). Context change andretention interval can have additive, rather than interactive,effects after taste aversion extinction. Psychonomic Bulletinand Review, 5, 79–83.

Rosas, J. M., Vila, N. J., Lugo, M., & López, L. (2001).Combined effect of context change and retention interval oninterference in causality judgment. Journal of ExperimentalPsychology: Animal Behavior Processes, 27, 153–164.

Rouder, J. N., Speckman, P. L., Sun, D., & Morey, R. D.(2009). Bayesian t-test for accepting and rejecting the nullhypothesis. Psychonomic Bulletin & Review, 16, 225–237.

Tamai, N., & Nakajima, S. (2000). Renewal of formerlyconditioned fear in rats after extensive extinction training.International Journal of Comparative Psychology, 13,137–147.

Thomas, B. L., Vurbic, D., & Novak, C. (2009). Extensiveextinction in multiple contexts eliminates the renewal ofconditioned fear in rats. Learning and Motivation, 40,147–159.

Urcelay, G. P., Wheeler, D. S., & Miller, R. R. (2009). Spacingextinction trials alleviates renewal and spontaneous recovery.Learning & Behavior, 37, 60–73.

Vansteenwegen, D., Hermans, D., Vervliet, B., Francken, G.,Beckers, T., Baeyens, F., & Eelen, P. (2005). Return of fearin a human differential conditioning paradigm caused by areturn to the original acquisition context. BehaviourResearch and Therapy, 43, 323–336.

Vansteenwegen, D., Vervliet, B., Iberico, C., Baeyens, F., Van denBergh,O.,&Hermans,D. (2007). The repeated confrontationwith videotapes of spiders in multiple contexts attenuatesrenewal of fear in spider-anxious students. BehaviourResearch and Therapy, 45, 1169–1179.

Vervliet, B., Baeyens, F., Van den Bergh, O., & Hermans, D.(in press). Extinction, generalization, and return of fear: Acritical review of renewal research in humans. BiologicalPsychology. http://dx.doi.org/10.1016/j.biopsycho.2012.01.006

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Laborda, M. & Miller, R. (2013). Preventing Return of Fear in an Animal Model of Anxiety. Additive...

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