Renewal of conditioned fear in male and female rats.

Pavlovian extinction reduces the performance of conditioned responses and occurs when the conditioned stimulus (CS) is repeatedly presented in the absence of the unconditioned stimulus (US). However, when the CS is experienced in a context that is different from the extinction context, there is a recovery of the conditioned response, a phenomenon known as renewal. There is some evidence that the renewal of appetitive conditioning is influenced by sex, with females failing to exhibit renewed responding. Further, there is recent evidence that renewal of fear might also not occur in female rats. In both appetitive and fear preparations, the lack of renewal in females has been postulated to be related to cycling ovarian hormones. Therefore, in Experiments 1 and 2, we directly compared fear renewal in males and females (Experiment 1) as well as ovariectomized (OVX) females (Experiment 2) when conditioning occurred in Context A, extinction in B, and testing in A (ABA renewal). Experiments 3 and 4 examined renewal when conditioning and extinction occurred in A and testing occurred in B (AAB renewal). In all experiments, renewal was not significantly different between male and female rats. Further, in Experiments 2 and 4, renewal did not differ between males, intact females, and OVX females. Additionally, in each experiment, there was no evidence that context excitation and/or inhibition contributed to renewal; instead suggesting that renewal was controlled by an occasion-setting mechanism. Overall, these results suggest little evidence for the role of sex in renewal of conditioned freezing and also indicate that cycling ovarian hormones have little role in the strength of renewal in female rats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of sex and retention interval on the retrieval and extinction of auditory fear conditioning.

Fear memory retrieval is relevant to psychiatric disorders such as post-traumatic stress disorder (PTSD). One of the hallmark symptoms of PTSD is the repeated retrieval and re-experiencing of the initial fear memory even long after the traumatic event has occurred. Women are nearly twice as likely to develop PTSD following a trauma than men, thus sex differences in the retrieval of fear memories is highly relevant for understanding the development and maintenance of PTSD. In the current study, we aimed to examine sex differences in the retrieval and extinction of either recent or remote fear memories. To do so, we conditioned male and female rats either 1 day (recent) or 28 days (remote) prior to testing retrieval and extinction. While there was no effect of sex or retention interval on initial retrieval, we found that remotely conditioned females exhibited higher rates of freezing than remotely conditioned males in later retrieval/extinction sessions, suggesting a sex difference in the retrieval and/or extinction of remote, but not recent, fear memories. Overall, these results are the first to demonstrate a sex difference in the extinction of remote fear memory, and this may contribute to the differential expression of fear-related disorders like PTSD in men and women.

Some Factors Modulating the Strength of Resurgence After Extinction of an Instrumental Behavior.

In resurgence, an operant behavior that has undergone extinction can return ("resurge") when a second operant that has replaced it itself undergoes extinction. The phenomenon may provide insight into relapse that may occur after incentive or contingency management therapies in humans. Three experiments with rats examined the impact of several variables on the strength of the resurgence effect. In each, pressing one lever (L1) was first reinforced and then extinguished while pressing a second, alternative, lever (L2) was now reinforced. When L2 responding was then itself extinguished, L1 responses resurged. Experiment 1 found that resurgence was especially strong after an extensive amount of L1 training (12 as opposed to 4 training sessions) and after L1 was reinforced on a random ratio schedule as opposed to a variable interval schedule that was matched on reinforcement rate. Experiment 2 found that after 12 initial sessions of L1 training, 4, 12, or 36 sessions of Phase 2 each allowed substantial (and apparently equivalent) resurgence. Experiment 3 found no effect of changing the identity of the reinforcer (from grain pellet to sucrose pellet or sucrose to grain) on the amount of resurgence. The results suggest that resurgence can be robust; in the natural world, an operant behavior with an extensive reinforcement history may still resurge after extensive incentive-based therapy. The results are discussed in terms of current explanations of the resurgence effect.

Effects of thinning the rate at which the alternative behavior is reinforced on resurgence of an extinguished instrumental response.

Three experiments with rats examined the effects of thinning the rate of reinforcement for the alternative behavior in the resurgence paradigm. In all experiments, pressing one lever (L1) was first reinforced and then extinguished while pressing a second alternative lever (L2) was then reinforced. When L2 responding was then extinguished, L1 responses "resurged." Resurgence was always observed when L2 was reinforced on an unchanging reinforcement schedule during Phase 2. However, other rats received systematic decreases in the rate of L2 reinforcement before extinction of L2 began. Such a "thinning" procedure was predicted to reduce final resurgence by associating L1 extinction with longer and longer periods without a reinforcer. The procedure did reduce the resurgence effect observed when L2 was put on extinction (Experiment 3). However, in each experiment, thinned groups also returned to L1 responding, and continued to make L1 responses, while the reinforcement schedule for L2 was being thinned. Fine-grained analysis of behavior in time suggested that this early resurgence was not due to adventitious reinforcement of L1, occasion setting of L1 by reinforcer presentation, or the entrainment of L1 as a schedule-induced interim behavior. The results are overall consistent with the hypothesis that resurgence is a renewal effect in which extinguished L1 responding recovers when the context provided by the L2 reinforcement schedule is changed. Challenges for this view are also discussed.

Relapse processes after the extinction of instrumental learning: renewal, resurgence, and reacquisition.

It is widely recognized that extinction (the procedure in which a Pavlovian conditioned stimulus or an instrumental action is repeatedly presented without its reinforcer) weakens behavior without erasing the original learning. Most of the experiments that support this claim have focused on several "relapse" effects that occur after Pavlovian extinction, which collectively suggest that the original learning is saved through extinction. However, although such effects do occur after instrumental extinction, they have not been explored there in as much detail. This article reviews recent research in our laboratory that has investigated three relapse effects that occur after the extinction of instrumental (operant) learning. In renewal, responding returns after extinction when the behavior is tested in a different context; in resurgence, responding recovers when a second response that has been reinforced during extinction of the first is itself put on extinction; and in rapid reacquisition, extinguished responding returns rapidly when the response is reinforced again. The results provide new insights into extinction and relapse, and are consistent with principles that have been developed to explain extinction and relapse as they occur after Pavlovian conditioning. Extinction of instrumental learning, like Pavlovian learning, involves new learning that is relatively dependent on the context for expression.

Effects of the amount of acquisition and contextual generalization on the renewal of instrumental behavior after extinction.

Four experiments with rat subjects examined the role of context during the extinction of instrumental (free-operant) behavior. In all experiments, leverpressing was first reinforced on a variable-interval 30-s schedule and then extinguished before being tested in the extinction and renewal contexts. The results identified three important variables affecting the renewal effect after instrumental extinction. First, ABA and ABC forms of renewal were strengthened by increasing the amount of acquisition training. This suggests that the strength of the association learned during acquisition, or the final level of performance, influences the degree of renewal after extinction. The effect of the amount of training was modulated by the second factor, the degrees of generalization from the acquisition and extinction contexts to the test context. The third variable was acquisition training in multiple contexts, which was shown to strengthen ABC renewal. Methodological, theoretical, and practical implications are discussed.

Contextual control of appetite. Renewal of inhibited food-seeking behavior in sated rats after extinction.

Obesity and overeating have become fundamental problems in modern society. This article studies the inhibition of food-seeking behavior, and how contextual cues can control it. Rats that had free food in the home cage nevertheless learned to lever press for sucrose or high-fat pellets in a distinctive context (a Skinner box). Lever pressing was then inhibited by extinction, in which lever presses no longer produced food. After extinction, inhibited responding was "renewed" when the rats were switched to a different context: in the new context, the rats lever-pressed again, and worked more for food when food was made available. These effects were observed when conditioning, extinction and testing occurred in contexts A, B, and A (respectively) or in A, A, and B. Thus, mere removal from the context in which food-seeking was inhibited initiated a return to food-seeking. The contextual control of extinction may help explain why food seeking and consumption seem so persistent.

Mechanisms of resurgence II: Response-contingent reinforcers can reinstate a second extinguished behavior.

Three experiments with rat subjects examined resurgence of an extinguished instrumental response using the procedure introduced by Epstein (1983) with pigeons. There were three phases: (1) initial acquisition of pressing on a lever (L1) for pellet reward, (2) extinction of L1, and (3) a test session in which a second lever (L2) was inserted, briefly reinforced, and then extinguished. Experiment 1 confirmed that if pressing L2 delivered 20 pellets followed by extinction, rats would resume L1 responding in the final test. Experiment 2 compared the effects of response-contingent and non-contingent rewards delivered upon insertion of L2. Although insertion of L2 alone did not increase L1 responding, response-contingent and non-contingent rewards led to comparable increases in L1 responding. Experiment 3 found that the delivery of non-contingent pellets during extinction of L1, which would be expected to reduce the ability of pellets to set the occasion for the L1 response, also reduced the effects of both response-contingent and non-contingent rewards during the final test. The results indicate that in this method, the resurgence treatment leads to an increase in L1 pressing due to simple presentation of the pellet; delivering the reinforcer after extinction of L1 reinstates L1 responding by setting the occasion for the L1 response.

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.

Mechanisms of resurgence of an extinguished instrumental behavior.

Four experiments examined "resurgence" of an instrumental behavior after extinction. All experiments involved three phases in which rats were (1) trained to press one lever for food reward, (2) trained to press a second lever while the first leverpress was extinguished, and (3) tested under conditions in which neither leverpress was rewarded. In each experiment, the first leverpress recovered (resurged) in Phase 3, when the second leverpress was extinguished. The results demonstrated that resurgence occurred when the schedules of reinforcement employed in Phases 1 and 2 yielded either an upshift, downshift, or no change in the rate of reward delivery between those phases. They also demonstrated that initial training on the first lever was required to observe a robust increase in pressing at test (resurgence is thus an associative effect). Resurgence was shown to occur over a wide variety of schedules of reinforcement in Phase 2 (including ratio, interval, and leverpress-independent schedules). Finally, the results do not support the view that resurgence occurs because response competition suppresses leverpressing of the first lever during extinction. Overall, they are consistent with the view that resurgence is a renewal effect in which extinction of an instrumental behavior is specific to the context provided by rewarded leverpressing during the extinction phase.

Interstimulus interval as a discriminative stimulus: evidence of the generality of a novel asymmetry in temporal discrimination learning.

Three appetitive conditioning experiments with rats examined temporal discrimination learning within Pavlovian conditioning trials. In all experiments, the duration of a feature white noise stimulus signaled whether or not a subsequent 10-s target tone would be reinforced. In Experiment 1, the feature durations were 4 and 1min. For one group of rats (Group 4+/1-), 4min of noise signaled that the tone would be reinforced and 1min of noise signaled that the tone would not be reinforced. A second group (Group 1+/4-) was trained with the reverse contingency. The results showed a clear asymmetry in temporal discrimination learning: rats trained with 4+/1- (Long+/Short-) learned the discrimination readily (responding more in the tone on reinforced than on nonreinforced trials), whereas rats trained with 1+/4- (Short+/Long) did not. In Experiment 2, the feature durations were shortened to 60 and 15s. Due to strong excitatory conditioning of the 15-s feature, the reverse asymmetry was observed, with the Short+/Long- discrimination learned more readily than the Long+/Short- discrimination. However, Experiment 3 demonstrated that the original Long+/Short- advantage could be recovered while using 60- and 15-s feature durations if the excitatory conditioning of the feature was reduced by including nonreinforced feature trials. The results support previous research involving the timing of intertrial intervals and are consistent with the temporal elements hypothesis which holds that the passage of time is encoded as a series of hypothetical stimulus elements.

Evidence of action sequence chunking in goal-directed instrumental conditioning and its dependence on the dorsomedial prefrontal cortex.

The current study investigated the contribution of the dorsomedial prefrontal cortex (dmPFC) to instrumental action selection. We found that cell body lesions of the dmPFC, centered on the medial agranular area, spared rats' ability to choose between actions based on either the value or the discriminative stimulus properties of an outcome. We next examined the effects of these lesions on action sequence learning using a concurrent bidirectional heterogeneous chain task in which the identity of the reward delivered was determined by the order in which the two lever press actions were performed. Although both lesioned rats and sham controls learned to perform the task, we found that they relied on different behavioral strategies to do so. In subsequent tests, rats in the sham group were able to withhold their performance of a sequence when either its associated outcome was devalued or the contingency between that sequence and its outcome was degraded by delivering the outcome noncontingently. Interestingly, lesioned rats failed to reorganize their performance at the action sequence level and, rather, were found to withhold their performance of the terminal response in the sequence that had earned the devalued outcome relative to the more distal response, suggesting that they represented the elements of the sequence as distinct behavioral units. These findings demonstrate that rats can use sequence-level representations, or action chunks, to organize their behavior in a goal-directed manner and indicate that the dmPFC plays a critical role in this process.

The influence of amphetamine on sensory and conditioned reinforcement: evidence for the re-selection hypothesis of dopamine function.

In four experiments we assessed the effect of systemic amphetamine on the ability of a stimulus paired with reward and a stimulus that was not paired with reward to support instrumental conditioning; i.e., we trained rats to press two levers, one followed by a stimulus that had been trained in a predictive relationship with a food outcome and the other by a stimulus unpaired with that reward. Here we show, in general accord with predictions from the dopamine re-selection hypothesis [Redgrave and Gurney (2006). Nat. Rev. Neurosci. 7, 967-975], that systemic amphetamine greatly enhanced the performance of lever press responses that delivered a visual stimulus whether that stimulus had been paired with reward or not. In contrast, amphetamine had no effect on the performance of responses on an inactive lever that had no stimulus consequences. These results support the notion that dopaminergic activity serves to mark or tag actions associated with stimulus change for subsequent selection (or re-selection) and stand against the more specific suggestion that dopaminergic activity is solely related to the prediction of reward.

Motivational control of second-order conditioning.

Two experiments examined the motivational specificity of the associations that support 2nd-order conditioning. In the 1st phase of each experiment rats were exposed to 2 visual conditioned stimuli (CSs) paired with either a saline or food pellet unconditioned stimulus (US) prior to exposure to 2nd-order conditioning using 2 auditory CSs, 1 paired with each visual CS. Rats' motivational state was then shifted prior to a test such that if and only if specific motivational features of the 1st-order training US played a role in the 2nd-order associative structure would responding to the 2nd-order cues shift appropriately with the state change. Even when the US was irrelevant to the training motivational state, shifts in state revealed that it was encoded within the associative structure supporting 2nd-order responding.