ABA Renewal Research Articles

Transient inactivation of the pigeon hippocampus or the nidopallium caudolaterale during extinction learning impairs extinction retrieval in an appetitive conditioning paradigm

The majority of experiments exploring context-dependent extinction learning employ Pavlovian fear conditioning in rodents. Since mechanisms of appetitive and aversive learning are known to differ at the neuronal level, we sought to investigate extinction learning in an appetitive setting. Working with pigeons, we established a within-subject ABA renewal paradigm based on Rescorla (Q J Exp Psychol 61:1793) and combined it with pharmacological interventions during extinction. From the fear conditioning literature, it is known that both prefrontal cortex and the hippocampus are core structures for context-specific extinction learning. Accordingly, we transiently inactivated the nidopallium caudolaterale (NCL, a functional analogue of mammalian prefrontal cortex) and the hippocampus in separate experiments by intracranial infusion of the sodium-channel blocker tetrodotoxin immediately before extinction training. We find that TTX in both structures non-specifically suppresses conditioned responding, as revealed by a reduction of response rate to both the extinguished conditioned stimulus and a control stimulus which remained reinforced throughout the experiment. Furthermore, TTX during extinction training impaired later extinction retrieval assessed under drug-free conditions. This was true when responding to the extinguished stimulus was assessed in the context of extinction but not when tested in the context of acquisition, although both contexts were matched with respect to their history of conditioning. These results indicate that both NCL and hippocampus are involved in extinction learning under appetitive conditions or, more specifically, in the consolidation of extinction memory, and that their contribution to extinction is context-specific.

Renewal of signaled shuttle box avoidance in rats

Five experiments with rats explored the renewal of acquired then extinguished avoidance behavior. Rats were individually trained to avoid signaled electric shock by crossing the midline of a shuttle box. Each midline crossing response stopped the auditory signal and cancelled the shock scheduled at the end of the signal. The midline crossing response was then extinguished by presenting the signal without the electric shock. Avoidance behavior was renewed when the rats were tested outside the extinction context. The rats were treated in 1 of 3 background contexts (A, B, and C) differing in multi-modal cues. The renewal of avoidance behavior was observed when the combination of acquisition, extinction, and test contexts was ABA, ABC, or AAB. The renewal amount was equivalent across the 3 paradigms, indicating that a critical factor in avoidance renewal is a release from the extinction context rather than a return to the acquisition context. The direct context–shock association seems to play a small role even in ABA renewal because repeated extra exposures to the acquisition context, which must have weakened the putative context–shock association, had little effect on the amount of ABA renewal.

Contrasting ABA, AAB and ABC renewal in a free operant procedure.

One experiment used a free operant procedure with rats to compare ABA, AAB and ABC renewal by using a within-subject testing procedure. All rats were first trained to press a lever for food in context A. Lever pressing was then extinguished in either context A or context B. For rats in the groups ABA and ABC extinction took place in context B, while the rats in group AAB received extinction in the same context in which acquisition took place (context A). Finally, all rats were tested for renewal in two sessions. One extinction session was carried out in the same extinction context and another session in a different context. Rats in the group ABA were tested in context B and in context A; rats in the group AAB were tested in contexts A and B, whereas the group ABC was tested in contexts B and C. The results of the ANOVA showed context renewal since all groups had higher rates of responding when they were tested outside the extinction context, F(2, 21) = 15.32, p = .001, ηp 2 = .59; however, AAB and ABC renewal was lesser than ABA renewal, F(1, 21) = 16.70, p = .0001, ηp 2 = .61.

An extinction retrieval cue attenuates renewal but not reacquisition of alcohol seeking.

The retrieval of extinction memories is dependent on contextual cues associated with extinction training. Various forms of response restoration after extinction, such as renewal, reinstatement, and spontaneous recovery, can be viewed as failures to retrieve an extinction memory. It follows that provision of a cue to aid retrieval of the extinction memory should attenuate response restoration or relapse after extinction. Six experiments studied the impact of an extinction retrieval cue (E-cue) on restoration of extinguished alcohol seeking in rats. Rats were trained to respond for alcoholic beer and this responding was then extinguished. Extinction training was accompanied by noncontingent presentations of a 60-s auditory stimulus that served as an E-cue. Presentations of the E-cue on test attenuated ABA renewal of alcohol seeking (Experiment 1) whereas an equally familiar cue from training had no effect (Experiment 2). Presentations of the E-cue had no effect on the reacquisition of alcohol seeking (Experiment 3). The same effects on ABA renewal (Experiments 4 and 6) and reacquisition (Experiment 5) were observed when the E-cue was trained in a response contingent manner during extinction. Taken together these findings show that presentations of an E-cue are able to attenuate the renewal but not reacquisition of alcohol seeking and are interpreted with reference to Bouton's model of extinction (Bouton, 1994a, 1994b, 2004).

Mechanisms of renewal after the extinction of discriminated operant behavior.

Three experiments demonstrated, and examined the mechanisms that underlie, the renewal of extinguished discriminated operant behavior. In Experiment 1, rats were trained to perform 1 response (lever press or chain pull) in the presence of one discriminative stimulus (S; light or tone) in Context A, and to perform the other response in the presence of the other S in Context B. Next, each of the original S/response combinations was extinguished in the alternate context. When the S/response combinations were tested back in the context in which they had been trained, responding in the presence of S returned (an ABA renewal effect was observed). This renewal could not be due to differential context-reinforcer associations, suggesting instead that the extinction context inhibits either the response and/or the effectiveness of the S. Consistent with the latter mechanism, in Experiment 2, ABA renewal was still observed when both the extinction and renewal contexts inhibited the same response. However, in Experiment 3, previous extinction of the response in the renewing context (occasioned by a different S) reduced AAB renewal more than did extinction of the different response. Taken together, the results suggest at least 2 mechanisms of renewal after instrumental extinction. First, extinction performance is at least partly controlled by a direct inhibitory association that is formed between the context and the response. Second, in the discriminated operant procedure, extinction performance can sometimes be partly controlled by a reduction in the effectiveness of the S in the extinction context. Renewal of discriminated operant behavior can be produced by a release from either of these forms of inhibition.

ABA renewal is greater when extinction occurs in the same context as cue pre-exposure.

Renewal has been observed in several protocols. One, termed ABA, trains a conditioned stimulus (CS) in one context, A, extinguishes the CS in a second context, B, and tests either in A or B. We used between- and within-subjects designs in three experiments with rats to study how a history of cue pre-exposure affects extinction and renewal of conditioned fear responses (freezing). In each experiment, a stimulus was pre-exposed in either context B or context C, paired with an aversive unconditioned stimulus (US) in a third context, A, extinguished in B, and finally tested in A. Freezing declined at the same rate when extinction occurred in the same or a different context as pre-exposure in between-subjects designs (Experiments 1 and 2), but declined faster when extinction and pre-exposure occurred in the same than in a different context in a within-subjects design (Experiment 3). In each experiment, renewal of freezing responses in the conditioning context, A, was greater when subjects were tested with the CS extinguished in its pre-exposure context than with the CS extinguished outside its pre-exposure context. The results were interpreted to mean that what was learned about the context-stimulus relation in pre-exposure enhanced control by that context over what was learned in extinction, thereby enhancing renewal when the rats were returned to the conditioning context for testing.

On the differences in degree of renewal produced by the different renewal designs

This paper addresses sources contributing to the differences in the degree of recovery from extinction observed with different renewal paradigms. In two lick suppression experiments with rats, we assessed the role of the associative status of the acquisition context in both the weakness of AAC renewal and the sometimes observed weaker renewal resulting from an ABC design relative to an ABA design. In Experiment 1, we observed that AAC renewal relative to an AAA control group was small unless Context A had undergone associative deflation (i.e., extinction of Context A). Deflation of Context A not only decreased behavioral control by the CS in the AAA condition, but increased it in the AAC condition, thereby implicating a comparator process in addition to associative summation between the CS and test context. In Experiment 2, an excitatory acquisition context was found to enhance the difference between ABC and ABA renewal. Associative deflation of the acquisition context decreased ABA renewal more than ABC renewal. Thus, the associative value of the acquisition context (A) was more positively related to the level of renewal when the target CS (X) was tested in this context than when it was tested in a neutral but equally familiar context (C), consistent with the frequently observed greater renewal in an ABA condition than an ABC condition arising from associative summation of the CS and test context. These findings demonstrate that the excitatory status of the acquisition context influences the observed degree of renewal.

A role for the ventral pallidum in context‐induced and primed reinstatement of alcohol seeking

The ventral pallidum (VP) is a major target of projections from the nucleus accumbens, and has been implicated in the reinstatement of psychostimulant seeking as part of a cortical-striatal-pallidal 'final common pathway' for relapse. Here, we studied the role of the VP in context-induced and primed reinstatement of alcoholic beer seeking, using a combination of microinjections and tract tracing studies. In experiment 1, rats were trained to respond to alcoholic beer in one context (A), and then extinguished in a second context (B), prior to testing for reinstatement (ABA renewal) and extinction (ABB). VP microinjection of the μ-opioid receptor (MOR) antagonist CTAP prevented reinstatement. In experiment 2, VP microinjection of CTAP also prevented the primed reinstatement of alcoholic beer seeking after rats were trained, extinguished, and tested in the same context. In experiment 3, we employed retrograde neural tract tracing together with c-Fos immunohistochemistry to identify the VP afferents recruited during context-induced reinstatement of alcoholic beer seeking. There was evidence for the recruitment of accumbens core→VP, basolateral amygdala→VP and paraventricular thalamus→VP pathways during context-induced reinstatement. These results indicate that the VP MORs are critical for context-induced reinstatement, and that the VP receives inputs from a number of regions known to be important in reinstatement of drug seeking.

Reacquisition, reinstatement, and renewal of a conditioned taste aversion in preweanling rats

Pavlovian extinction is defined as a reduction of the conditioned response (CR) as a consequence of repeated and nonreinforced presentations of the conditioned stimulus (CS). This phenomenon has been explained through two nonexclusive associative hypotheses. One of them proposes that the CS-unconditioned stimulus (US) association is weakened during extinction, while the second one explains extinction by the formation of a new inhibitory association between the CS, and the US (CS-noUS) which competes with the excitatory one acquired at conditioning (CS-US). Research supporting this second hypothesis is based on the demonstration that the CR can be recovered after extinction. However, in preweanling rats, renewal, and reinstatement treatments have failed to recover a conditioned fear response, suggesting that extinction during this ontogenetic period may involve erasure of the CS-US association. The goal of the present study was to explore whether this conclusion can be extended to the extinction of a conditioned taste aversion by evaluating infant rats in three different procedures (reacquisition, ABA renewal, and reinstatement). The results are consistent with the idea that extinction of a taste aversive memory during infancy involves relearning about the relationship between the CS and the US, with the initial CS-US association remaining relatively intact. Extinction of a taste aversive memory and a fear memory may involve different biological mechanisms during infancy. The conclusion that the only psychological mechanism for extinction during infancy is unlearning should be confined to a particular type of memory.

ABA and ABC renewal of conditioned magazine approach are not impaired by dorsal hippocampus inactivation or lesions

Three experiments investigated the role of the dorsal hippocampus (DH) in renewal of conditioned and then extinguished magazine approach responding in rats. Experiments 1 and 2 found no effect of muscimol inactivation of the DH during testing on ABA and ABC renewal, respectively. However, subjects from these studies were subsequently found to be impaired on a delayed non-matching-to-place task following muscimol but not saline infusions. Experiment 3 found no effects of post-training excitotoxic lesions of the DH on ABA and ABC renewal. Lesioned subjects were, however, impaired on the delayed non-matching-to-place task compared to control subjects. These findings suggest that the DH may not play a similar role in Pavlovian extinction in appetitive learning tasks as has previously been reported in aversive learning.

The informational value of contexts affects context-dependent learning

In two predictive-learning experiments, we investigated the role of the informational value of contexts for the formation of context-dependent behavior. During Phase 1 of each experiment, participants received either a conditional discrimination in which contexts were relevant (Group Relevant) or a simple discrimination in which contexts were irrelevant (Group Irrelevant). Each experiment also included an ABA renewal procedure. Participants received Z+ in context A during Phase 1, extinction of Z in context B during Phase 2, and were tested with Z in context A during a test phase. In each experiment, extinction of Z proceeded faster and was followed by stronger response recovery in Group Relevant than in Group Irrelevant. In Experiment 2, which included recording of eye-gaze behavior, dwell times on contexts were longer in Group Relevant than in Group Irrelevant. Our results support the idea that relevant contexts receive more attention, leading to stronger context specificity of learning.

Extinction of reinstated or ABC renewed fear responses renders them resistant to subsequent ABA renewal.

Three experiments used an ABA renewal paradigm to study deepening of response loss produced by extinction of reinstated or ABC renewed fear responses. In Experiment 1, rats were trained with two stimuli, S1 and S2, in context A and extinguished to S1 in context B and S2 in context C, shocked in B but not in C, and subjected to additional extinction of S1 in B and S2 in C. Rats froze less to S1 than S2 when subsequently tested in A. In Experiments 2 and 3, following training of S1 and S2 in A, one group received extinction of S1 in B and S2 in C followed by extinction of S1 in C and S2 in B. This group froze less to S1 in A or to S2 in a novel context, D, than a group always extinguished to S1 in B and S2 in C or a group extinguished to both S1 and S2 in B and C. These results show that additional extinction of a conditioned stimulus (conditional stimulus [CS]) exhibiting either reinstatement or ABC renewal renders that CS resistant to ABA renewal. They are consistent with theories that allow a role for context in extinction learning and that use error-correction mechanisms to update this learning.

μ-Opioid receptors in the nucleus accumbens shell mediate context-induced reinstatement (renewal) but not primed reinstatement of extinguished alcohol seeking.

Opioid antagonists reduce the rate of relapse to drinking in clinical trials and reduce reinstatement in animal models of drug seeking. However, the neuroanatomical locus for this effect remains poorly understood. We examined the role of nucleus accumbens shell (AcbSh) μ-opioid receptors in two different forms of recovery of alcoholic beer seeking. Rats were trained to nosepoke for alcoholic beer in a distinctive context and this response was then extinguished. Response recovery was produced via renewal (context-induced reinstatement) (Experiment 1) or primed reinstatement (Experiment 2). Rats received microinjections of the μ-opioid receptor antagonist CTAP before these tests. AcbSh microinfusion of 2.5 μg CTAP attenuated the ABA renewal of alcoholic beer seeking in a neuroanatomically specific manner. In contrast, AcbSh microinfusion of 2.5 μg or 5 μg CTAP had no effect on the primed reinstatement of alcoholic beer seeking. These findings indicate a role for AcbSh μ-opioid receptors in renewal of alcoholic beer seeking and suggest that there are dissociable ventral striatal substrates for different forms of recovery of extinguished alcoholic beer seeking.

The role of medial prefrontal cortex in extinction and reinstatement of alcohol‐seeking in rats

The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer-seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug-seeking. Rather, they support the view that PL is important for retrieval of drug-seeking contingency information and that the use of contextual information is enhanced with IL manipulation.

Extinction treatment in multiple contexts attenuates ABC renewal in humans

Renewal has been implicated as one of the underlying mechanisms in return of fear following exposure therapy. ABC renewal is clinically more relevant than ABA renewal and yet it is a weaker form of renewal, suggesting that conducting extinction treatment in multiple contexts may be sufficient to attenuate ABC renewal. Using self-reported expectancy of shock and startle blink responses the current study examined the effects of conducting extinction treatment in multiple contexts on ABC fear renewal. Participants (N = 68) received conditional stimulus (CS) and unconditional stimulus (US) pairings in one context (A) followed by extinction treatment (CS presentations alone) in either one other context (B) or three other contexts (BCD). Non-reinforced test trials in a novel context (E) resulted in renewal of extinguished conditioned behaviour for those who received extinction in only one context. However, renewal was attenuated for those who received extinction treatment in three contexts. No renewal was found for the control group that received the test trial in the same context as during extinction. Suggestions are provided for clinicians seeking to prevent or attenuate return of fear following exposure therapy.

RESISTANCE TO CHANGE AND RELAPSE OF OBSERVING

Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI schedule (i.e., S+). The components differed in the rate of food arranged (Rich = VI 30 s; Lean = VI 120 s). In Experiment 1, following baseline training, extinction of observing involved removal of both food and S+ deliveries, and reinstatement was examined by presenting either response-independent food or S+ deliveries. In Experiment 2, extinction involved removal of only food deliveries while observing responses continued to produce S+. Reinstatement was examined by delivering food contingent upon the first two food-key responses occurring in the presence of the S+. Experiment 3 assessed ABA renewal of observing by extinguishing food-key and observing responses in the presence of one contextual stimulus (i.e., B) and then returning to the original training context (i.e., A) during continued extinction. Experiment 4 examined resurgence by introducing food reinforcement for an alternative response during extinction, and subsequently removing that alternative source of food. Across experiments, relative resistance to extinction and relapse of observing tended to be greater in the component previously associated with the higher rate of primary reinforcement. Relapse of observing or attending to stimuli associated with primary reinforcement appears to be impacted by frequency of primary reinforcement in a manner similar to responding maintained directly by primary reinforcement.

A modified counterconditioning procedure prevents the renewal of conditioned fear in rats

Two studies using an ABA design examined the Extinction and renewal of conditioned barpress suppression. Following lights-off and foot shock pairings in Context A, rats were placed in Context B and were given either a standard counterconditioning procedure where the lights-off CS was paired with a novel food US delivered freely or a modified counterconditioning procedure where CS-US pairings only occurred if the rat earned the US by performing a required behavior during the CS. Results indicated that the modified counterconditioning procedure thwarted ABA renewal but the conventional counterconditioning procedure did not reduce ABA renewal any more than nonreinforced exposure to the CS alone. Furthermore, the response required during the modified counterconditioning procedure could be one used as a baseline response during Acquisition of fear or it could be a novel response. Implications of the results for theories of Extinction and renewal of fear are discussed.

Adding imagery rescripting during extinction leads to less ABA renewal

Objective Although extinction is highly effective in reducing a conditioned fear response, return of the fear response (renewal) outside the extinction context often occurs. The present study investigated whether US devaluation, through imagery rescripting during extinction, resulted in less renewal than mere extinction. Method Seventy psychology students were subjected to a fear conditioning paradigm. During fear acquisition CS+ was always followed by the US, whereas CS− was never followed by the US. For all groups the acquisition phase took place in context A. During extinction both CS+ and CS− were offered, but no US was presented. For three groups extinction was conducted in a different context, context B (ABA groups). The fourth group received extinction in the acquisition context (AAA group) in order to demonstrate that renewal indeed took place. During extinction, participants received either an imagery rescripting (IR) instruction to devaluate the US (ABAir), a US-unrelated imagination instruction to assess the general influence of imagination (ABAcont), or no instruction at all (ABAno and AAAno). Subsequently, testing occurred for all groups in the acquisition context A. Results The results indicated that renewal of the US expectancy ratings was reduced if imagery rescripting (ABAir) was added to mere extinction (ABAno). Next to the reduction in renewal, imagery rescripting (ABAir) also resulted in the devaluation of the US valence, indicating that the mental representation of the US had changed. These findings are not only in line with contemporary conditioning theories, but also suggest that adding imagery rescripting to extinction might be beneficial in the treatment of anxiety problems.

Renewal after the extinction of free operant behavior

Four experiments were performed to explore the role of context in operant extinction. In all experiments, leverpressing in rats was first reinforced with food pellets on a variable interval 30-s schedule, then extinguished, and finally tested in the same and a different physical context. The experiments demonstrated a clear ABA renewal effect, a recovery of extinguished responding when conditioning, extinction, and testing occurred in contexts A, B, and A, respectively. They also demonstrated ABC renewal (where conditioning extinction and testing occurred in contexts A, B, and C) and, for the first time in operant conditioning, AAB renewal (where conditioning, extinction, and testing occurred in contexts A, A, and B). The latter two phenomena indicate that tests outside the extinction context are sufficient to cause a recovery of extinguished operant behavior and, thus, that operant extinction, like Pavlovian extinction, is relatively specific to the context in which it is learned. AAB renewal was not weakened by tripling the amount of extinction training. ABA renewal was stronger than AAB, but not merely because of context A's direct association with the reinforcer.

Effects of D-cycloserine on the extinction of appetitive operant learning.

Four experiments with rat subjects examined whether D-cycloserine (DCS), a partial NMDA agonist, facilitates the extinction of operant lever-pressing reinforced by food. Previous research has demonstrated that DCS facilitates extinction learning with methods that involve Pavlovian extinction. In the current experiments, operant conditioning occurred in Context A, extinction in Context B, and then testing occurred in both the extinction and conditioning contexts. Experiments 1A and 1B tested the effects of three doses of DCS (5, 15, and 30 mg/kg) on the extinction of lever pressing trained as a free operant. Experiment 2 examined their effects when extinction of the free operant was conducted in the presence of nonresponse-contingent deliveries of the reinforcer (that theoretically reduced the role of generalization decrement in suppressing responding). Experiment 3 examined their effects on extinction of a discriminated operant, that is, one that had been reinforced in the presence of a discriminative stimulus, but not in its absence. A strong ABA renewal effect was observed in all four experiments during testing. However, despite the use of DCS doses and a drug administration procedure that facilitates the extinction of Pavlovian learning, there was no evidence in any experiment that DCS facilitated operant extinction learning assessed in either the extinction or the conditioning context. DCS may primarily facilitate learning processes that underlie Pavlovian, rather than purely operant, extinction.