Extinction of Within-event Learning Is Contextually Controlled and Subject to Renewal

Five experiments examined within-event learning in rats by inducing an appetite for one of the elements (salt) of a compound stimulus and assessing preference for the other element (almond). Almond preference was conditional upon (1) the almond flavour having been presented in compound with the salt, and (2) the assessment being conducted when the rats were out of sodium balance (Experiment 1). Presentations of the compound in one environment (A) and of the salt and almond elements in a second environment (B) resulted in greater almond preference when rats were tested in A than in B (Experiment 2). Almond preference was reduced when separate presentations of the compound and almond (Experiment 3) or of the compound and salt (Experiment 4) occurred in the same environments but not when these presentations occurred in different environments. Rats exposed to the compound in A and then extinguished to the elements in either A or B showed a reduced almond preference when tested in the extinction environment, but not when tested in the other environment (Experiment 5). Thus, extinction of within-event learning is context-specific and subject to renewal. The results were interpreted in terms of an associative model whereby separate presentations of the elements result in a symmetrical inhibitory link which is contextually gated (Bouton, 1993).     

Expression of flavor preference depends on type of test and on recent drinking history

The persistence of a conditioned flavor preference was examined in 3 experiments. All contained an initial acquisition phase in which half the rats were given almond odor mixed with sucrose (AS) in some sessions and water (W) only in other sessions, whereas the other half (controls) were given explicitly unpaired exposures to almond (A) and sucrose (S) in separate sessions. Subsequent 2-bottle choice tests revealed a persistent preference for A, despite extinction exposure to A or S, but this depended on the choice offered on test: Exposure to A did not extinguish the preference for A over W but did reduce the preference for AS over S; conversely, exposure to S did not extinguish the preference for AS over S but did reduce the preference for A over W. These results indicate that flavor preferences can be resistant to extinction procedures but suggest that the expression of such preferences in choice tests depends on an adaptation-level process.     

Persistence of conditioned flavor preferences is not due to inadvertent food reinforcement

Almond preferences were produced by giving rats a mixture of almond and sucrose (Experiments 1-4) or saccharin (Experiment 4). A subsequent extinction procedure consisted of either repeated 2-bottle almond versus water tests (Experiment 1) or repeated exposure to almond alone (Experiments 2-4). The main independent variable was whether access to food following a session was given immediately, 30 min later, or 120 min later. No effect of extinction was found in any experiment. An important finding was that varying the delay until food access had no detectable effect. It was concluded that inadvertent flavor-food associations do not maintain preference for the flavor under extinction conditions.     

Differences between golden hamsters (Mesocricetus auratus) and Norway rats (Rattus norvegicus) in preference for the sole diet that they are eating

D. DiBattista (2002) reported that hamsters but not rats showed reduced preferences for the sole diet they had eaten for 10 days. In the current study, the authors fed Norway rats (Rattus norvegicus) a nutritious diet for either 3 or 10 days, then tested them either immediately or 1 or 3 days later. The authors found that like golden hamsters (Mesocricetus auratus), rats exhibited reduced preferences for a prefed diet but only if tested either immediately or 1 day after prefeeding, not if tested 3 days later (when D. DiBattista tested his hamsters). Rats and hamsters differed in the longevity, not the development, of reduced preferences for a palatable food eaten for several consecutive days. Such a response might aid dietary generalists in constructing balanced diets when no single available food is nutritionally adequate.     

The benzodiazepine midazolam does not impair Pavlovian fear conditioning but regulates when and where fear is expressed.

Rats were injected with a benzodiazepine (midazolam) and shocked after presentation of an auditory conditioned stimulus (CS). They were then tested for fear reactions (freezing) to the CS in either the original context or a 2nd context after either a short (1-day) or long (21-day) retention interval. Rats tested in the original context froze less after 1 day than rats tested after that interval in the 2nd context or rats tested after 21 days. Moreover, rats tested after the long interval in the original context froze less than rats tested after that interval in the 2nd context. Therefore, midazolam does not impair the acquisition of conditioned fear but regulates when and where that fear is expressed. These effects of midazolam were interpreted as a contextually controlled deficit in the expression of conditioned fear that is similar to that associated with latent inhibition and extinction (M. E. Bouton, 1993).     

Extinction of the context and latent inhibition

The hypothesis that latent inhibition could be reduced by extinguishing the experimental context, that is, exposing the rats to the context between exposure to the conditional stimulus (CS) and conditioning, was tested. All experiments used the conditioned emotional response procedure. In Experiment 1, extinction was not effective when the animals were exposed to the clicker 40 times off the baseline of responding for food and when the clicker CS was partially reinforced with shocks during the test phase. In Experiments 2 and 3, latent inhibition could be reduced by extinction if the animals were exposed to the CS 24 or 16 times on-baseline, and if continuous reinforcement was used during the test. In Experiments 4, 5, and 6, we attempted to determine which variable was responsible for the discrepant results. In Experiment 4, extinction was effective with 20 or 40 on-baseline exposures to the CS, using continuous reinforcement during the test. In Experiment 5, extinction was not effective with exposure on- or off-baseline, using 24 exposures and partial reinforcement. Finally, in Experiment 6, extinction reduced latent inhibition using continuous, but not partial, reinforcement with 40 exposures off-baseline. From these results, we concluded that Wagner's model of habituation was not sufficient to account for latent inhibition and that a hybrid model, using both associative and cognitive representational processes, was necessary.     

D-cycloserine facilitates context-specific fear extinction learning

D-cycloserine (DCS) may facilitate fear extinction learning, but the behavioral consequences and mechanisms behind this effect are not well understood at present. In this paper, we re-analyze data from previously reported null result experiments and find that rats showing above-median extinction learning during DCS treatment benefited from the drug, whereas rats showing below-median (and in this case little) extinction learning did not. Two additional experiments found that DCS facilitated extinction learning when specifically combined with a moderate, but not a small, number of extinction trials. DCS thus facilitates extinction learning only if the behavioral procedure first engages the extinction learning process. The benefits of the drug, however, were specific to the context in which extinction was learned--i.e., DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.     

Dissociative effects of different types and amounts of nonreinforced CS exposure on avoidance extinction and the CER

Two experiments examined the effectiveness of two amounts of flooding or response-prevention on hastening avoidance response extinction and on reducing CS-produced suppression of bar-pressing for food. In Experiment 1, 20 and 30 flooding trials were both shown to be effective in hastening the extinction of a well-learned shuttlebox avoidance response. In Experiment 2, rats trained under comparable conditions to those in Experiment 1 were tested following flooding for the CER in a different apparatus. The results indicated that 30, but not 20, flooding trials were sufficient to reduce the CER. In each experiment the results of additional control groups equated with the flooded groups for nonreinforced CS exposure also revealed a dissociation between the effectiveness of this CS time control procedure in hastening avoidance response extinction and in reducing the CER. Further comparisons showed that although 30 flooding trials did reduce the CER, the same total duration of nonreinforced CS Exposure in the form of avoidance extinction trials did not. Thus the context in which CS exposure occurs may affect the dynamics of extinction of the CER. The experiments are discussed in the broader context of dissociation of various indices of fear in humans.     

Reinstatement of fear to an extinguished conditioned stimulus: two roles for context

The authors studied the role of context in reinstatement. Freezing was reinstated when the conditioned stimulus (CS) was extinguished in 1 context and rats moved to another context for reexposure to the shock unconditioned stimulus (US) and test. It was also reinstated (rather than renewed) when rats were shocked in the extinction context and moved to another context for test. This reinstatement was CS specific and reduced by nonreinforced exposures to the extinction context. Rats shocked in the context in which a stimulus had been preexposed froze when tested in another context. These findings suggest 2 roles for context in reinstatement: conditioning of the test context (M. E. Bouton, 1993) and mediated conditioning by the extinction context (P. C. Holland, 1990).     

Extensive extinction in multiple contexts eliminates the renewal of conditioned fear in rats

Two studies examined whether nonreinforcement of a stimulus in multiple contexts, instead of a single context, would decrease renewal of conditioned fear in rats (as assessed by conditioned suppression of lever pressing). In Experiment 1, renewal was measured after 36 nonreinforced CS trials delivered during six extinction sessions in a single context or two extinction sessions in each of three different contexts. The number of extinction contexts did not have an effect on renewal. In Experiment 2, groups received either 36 or 144 nonreinforced CS trials during six or twenty-four extinction sessions in a single context or three different contexts. Again, renewal was not influenced by the number of extinction contexts when only 36 trials were given. However, when 144 trials were used, renewal was completely eliminated when extinction was divided between 3 contexts, but was not weakened when the sessions took place in a single context. The results suggest that the use of multiple treatment settings in exposure-based therapies is only likely to reduce relapse if a sufficient number of sessions are provided in each of the treatment settings.     

Developmental flavor experience affects utilization of odor, not taste in toxiphobic conditioning

Feeding experiences were varied in developing rats and the effects upon flavor neophobia and lithium chloride-induced flavor aversions were observed. In Experiment 1, nursing experience of neonate rats was reduced by artificial feeding via intragastric cannula; the rats then were tested with apple juice paired with lithium chloride injection at weaning or maturity. Conditioned aversions were not affected, but neophobia to novel apple juice was attenuated in artificially-reared rats tested at maturity. In Experiment 2, rats received enriched feeding experience after weaning, which consisted of (a) obtaining many complex flavors, a few of which were paired with poisoning, effortlessly in the home cage, or (b) foraging for various foods on an elevated maze. No dramatic effects on neophobia or conditioned taste aversion for saccharin water were apparent. In Experiment 3, rats were given experience after weaning with vanilla-scented water either paired or unpaired with quinine water, and then tested with the odor of almond or that odor compounded with saccharin water for neophobia and lithium-induced aversions. Flavor-experienced rats exhibited more pronounced odor conditioning and more resistance to extinction of the odor aversion after both simple and compound conditioning. In contrast, saccharin taste aversions were relatively unchanged. Apparently, enriched feeding and drinking experience facilitates the utilization of odor more than taste cues.     

Short- and long-term decrements in toxicosis-induced odor-aversion learning: the role of duration of exposure to an odor

Six experiments employed an odor-aversion paradigm to investigate the role of the duration of exposure to an odor in determining that odor's subsequent associability with illness. Rats were exposed to an odor at times T1 and T2, and the second of these exposures was followed by toxicosis. When the initial odor exposure was brief, the odor aversion was attenuated with a moderate T1-T2 interval of 3 hr (Experiment 1) but not with long intervals of 28 hr and 76 hr (Experiment 2). In contrast, when the initial odor exposure was long, the odor aversion was attenuated at a long T1-T2 interval (Experiment 3). With a T1-T2 interval of 24 hr, a brief initial exposure did not attenuate odor aversions when the context either remained the same or was changed from T1 to T2, whereas a long initial exposure attenuated such aversions when the context remained the same but not when the context was changed (Experiment 4). With a T1-T2 interval of 3 hr, a brief initial exposure attenuated odor aversions when the context remained the same or was changed from T1 to T2, whereas a long initial exposure attenuated such aversions when the context remained the same but not when the context was changed (Experiment 5). A brief exposure at T1, either with or without a subsequent context "extinction," attenuated odor aversions when the T1-T2 interval was 3 hr but not when this interval was 24 hr; a long initial exposure at T1, without a subsequent context "extinction," attenuated odor aversions when the T1-T2 interval was 4 hr and 24 hr but with a subsequent context "extinction" did not attenuate such aversions at either 4-hr or 24-hr T1-T2 intervals (Experiment 6). The results demonstrate that the duration of exposure to an odor determined whether that odor presentation caused short- or long-term decrements in odor conditionability and are discussed in terms of the relation between self- and retrieval-generated processes.     

The effects of context extinction on US signal value

Two experiments with rats examined the effects of context extinction on responding to the signal value of an unconditioned stimulus (US). In Experiment 1, US signal value was first trained when a single food pellet signaled the delivery of three additional pellets. After training, rats received either context extinction (CE) or home cage (HC) exposure before testing US signal value by single food pellet presentations. Results showed responding was significantly reduced in Group CE compared to Group HC. Experiment 2 replicated Experiment 1 and showed that exposure to a different context did not reduce responding to the signal value of a US. The results complement research by Kehoe et al. [Kehoe, E. J., Weidemann, G., & Dartnall, S. (2004). Apparatus exposure produces profound declines in conditioned nictitating-membrane responses to discrete conditioned stimuli by the rabbit (Oryctolagus cuniculus). Journal of Experimental Psychology: Animal Behavior Processes, 30, 259–270.] and have key implications for prominent theories of conditioning.     

Effects of multiple exposures to D-cycloserine on extinction of conditioned fear in rats

Previous research has shown that an acute, post-training injection of D-cycloserine (DCS) facilitates extinction of conditioned fear in rats; however, the effects of multiple exposures to DCS in this situation are not known. In Experiment 1, rats were conditioned (light-shock pairings) and 24 h later given six extinction (light-alone) trials followed by an injection of DCS (15 mg/kg) or saline. The next day, all rats were tested for light-elicited freezing. In Experiment 2, the effect of DCS on extinction was tested in the same manner, except that rats were pre-exposed to DCS (0, 1, or 5 injections) just prior to conditioning. In Experiment 3, rats received five pre-exposures of DCS but conditioning occurred either 2 or 28 days after the last pre-exposure. The results showed that DCS facilitated extinction of conditioned freezing to the light CS when no drug pre-exposure had occurred, but pre-exposure to DCS just prior to conditioning disrupted the facilitation of extinction effect. When 28 days were interposed between pre-exposure and conditioning, the facilitatory effects of DCS on extinction were restored. These findings suggest that DCS has significant clinical value but that behavioral desensitization may occur with multiple exposures; however, desensitization is not permanent and is reduced by the passage of time.     

Accumbens shell AMPA receptors mediate expression of extinguished reward seeking through interactions with basolateral amygdala

Extinction is the reduction in drug seeking when the contingency between drug seeking behavior and the delivery of drug reward is broken. Here, we investigated a role for the nucleus accumbens shell (AcbSh). Rats were trained to respond for 4% (v/v) alcoholic beer in one context (Context A) followed by extinction in a second context (Context B). Rats were subsequently tested in the training context, A (ABA), or the extinction context, B (ABB). Pre-test injections of the glutamate AMPA receptor antagonist, NBQX (1 μg) into AcbSh had no effect on renewal of alcoholic beer seeking when rats were returned to the training context (ABA). However, NBQX increased responding when rats were tested in the extinction context (ABB). In a second experiment, rats received training, extinction, and test in the same context. Pre-test injections of NBQX (0, 0.3, and 1 μg) into the AcbSh dose-dependently attenuated expression of extinction. We also found that NBQX in the AcbSh had no effect on initial acquisition of extinction or the motivation to respond for reward as measured by break point on a progressive ratio schedule. Finally, we show that pharmacological disconnection of a basolateral amygdala (BLA) → AcbSh pathway via NBQX in AcbSh combined with reversible inactivation of the contralateral BLA attenuates expression of extinction. Together, these results suggest that AcbSh AMPA receptors mediate expression of extinguished reward seeking through glutamatergic inputs from the BLA.     

Anisomycin infused into the hippocampus fails to block "reconsolidation" but impairs extinction: the role of re-exposure duration

Recent studies have reported new evidence consistent with the hypothesis that reactivating a memory by re-exposure to a training context destabilizes the memory and induces "reconsolidation." In the present experiments, rats' memory for inhibitory avoidance (IA) training was tested 6 h (Test 1), 2 d (Test 2), and 6 d (Test 3) after training. On Test 1 the rats were either removed from the shock compartment immediately after entry or retained in the shock context for 200 sec, and intrahippocampal infusions of the protein synthesis inhibitor anisomycin (75 microg/side) were administered immediately after the test. Anisomycin infusions administered after Test 1 impaired IA performance on Test 2 in animals given the brief re-exposure, but impaired extinction in animals exposed to the context for 200 sec. Rats with anisomycin-induced retention impairment on Test 2 demonstrated spontaneous recovery of retention performance on Test 3, whereas rats showing extinction on Test 2 showed further extinction on Test 3. The findings indicate that post-retrieval administration of anisomycin impairs subsequent retention performance only in the absence of extinction and that this impairment is temporary.     

Relapse of operant behavior after response elimination with an extinction or an omission contingency

The present study compared relapse after responding was eliminated by extinction or omission training in rats. In Experiment 1, lever pressing was reinforced with food pellets in Context A and then eliminated with either extinction or omission training in Context B. The response was then tested in Contexts A and B in either the presence or absence of free food pellets delivered on a random time schedule. All rats showed higher responding when tested in Context A than Context B, and there was little evidence that omission training attenuated this ABA renewal effect. Noncontingent pellets increased responding after extinction but not after omission. However, when responding on the last day of response elimination was compared to responding during the test in the response-elimination context, there was some evidence that omission-trained rats showed a small increase in responding even when tested with free pellets. Results of Experiment 2 suggest this increase was not due to differences in the temporal distribution of pellets during elimination and the test, and that the result might be due to mere removal of the omission contingency, but any such effect is small and difficult to detect statistically. The results provide new information about factors generating relapse after omission training.     

d-Serine facilitates the effects of extinction to reduce cocaine-primed reinstatement of drug-seeking behavior

Male Sprague Dawley rats were allowed to self-administer cocaine (0.5 mg/kg) during 90 min sessions for a period of 15 days. On day 16, rats were either held abstinent in their home cage environment or experienced an extinction session in which the active lever had no programmed consequences. Facilitating N-methyl-d-aspartate (NMDA) receptor activity with the coagonist d-serine (100 mg/kg i.p.) before or following the extinction session significantly reduced the subsequent cocaine-primed reinstatement of drug-seeking behavior tested on day 17. d-Serine significantly reduced drug-primed reinstatement only when combined with extinction, and its effectiveness when administered following the training session suggested that an enhancement of consolidation of extinction learning had occurred. In contrast, d-serine treatment did not reduce sucrose-primed reinstatement, indicating that the beneficial effects of this adjunct pharmacotherapy with extinction training were specific to an addictive substance (cocaine) and did not generalize to a natural reward (sucrose).     

Mechanisms of blocking by contextual stimuli

The influence of contextual stimuli on the conditioning and performance of responding to a discrete stimulus was examined in the US preexposure paradigm using both context shift manipulations and a measure of context conditioning. Four groups of rats received both repeated exposure to an electric shock US in one context (Context 1), and repeated nonshocked exposure to a second context (Context 2). Two additional groups of rats received exposure to these contexts, but never received shock presentations. Rats exposed to shock learned to escape from the stimuli of Context 1, but did not escape from the stimuli provided by Context 2. Rats not exposed to shock failed to escape from either context. All rats then received a single CER conditioning session in which four pairings of a 3-min noise CS and shock US were presented. Half the rats received those CS-US pairings in the excitatory Context 1, while the remaining rats received those pairings in the neutral Context 2. Finally, half the rats in each of the CER conditioning treatments received extinction test trials of the noise CS in Context 1, while the remaining rats received those test trials in Context 2. Thus, this design factorially manipulated the presence of excitatory or neutral contextual stimuli during both conditioning and testing of a discrete CS. In comparison with the two groups of rats never preexposed to shock alone, attenuation in acquisition of conditioned suppression observed during test trials occurred only when CER conditioning had been administered in the excitatory Context 1, and this effect was manifested when testing occurred in either the excitatory Context 1 or the neutral Context 2. These results support the model of R. A. Rescorla and A. R. Wagner (1972) (in A. H. Black & W. F. Prokasy (Eds.) Classical Conditioning II, pp. 64–99, New York: Appleton-Century-Crofts) which asserts that contextual stimuli and sicrete CSs compete for limited associative strength supportable by a given US.     

Extinction in multiple contexts does not necessarily make extinction less vulnerable to relapse

Three fear-conditioning experiments with rat subjects examined the effects of extinction in multiple contexts on a final relapse (renewal) effect that occurred when the extinguished fear cue was tested in a new context (Experiments 1 and 3) or in the context in which fear conditioning had first occurred (Experiment 2). Rats that received extinction in three contexts demonstrated more fear during extinction than rats that received the same number and temporal distribution of extinction trials in one context; extinction was partially lost with each context switch. Although extinction in multiple contexts thus had an impact on extinction behavior, it did not reduce the size of the final renewal effect. Fear during extinction was occasionally positively correlated with fear during final testing, but the two were never negatively correlated. The results suggest that extinction in multiple contexts does not necessarily weaken fear renewal, and that extinction procedures that generate high levels of responding in extinction do not necessarily make extinction learning less context-specific.