No abstract

Resurgence has commonly been viewed as the recovery of an extinguished instrumental behavior that occurs when an alternative behavior that has replaced it is also extinguished. Three experiments with rat subjects examined the effects on resurgence of the temporal distribution of reinforcement for the alternative behavior that is presented while the first response is being eliminated. Experiments 1 and 2 examined resurgence when rich rates of reinforcement at the onset of response elimination became leaner over sessions (i.e., forward thinning) and when lean rates became richer (i.e., reverse thinning). Both procedures weakened resurgence compared to that in a group that received the richest rate during all sessions. However, forward thinning was more effective than reverse thinning at reducing the resurgence effect. Experiment 3 found that final resurgence was eliminated when the alternative behavior was reinforced and extinguished in alternating response elimination sessions. The results are consistent with the hypothesis that reinforcer delivery during response elimination provides a contextual stimulus for the extinction of the original behavior; its removal during resurgence testing causes ABC renewal to occur. The results are less consistent with an alternative account that emphasizes the removal of response disruption caused by alternative reinforcement (Shahan & Sweeney, 2011). Other theoretical and applied implications are discussed.

In resurgence, an extinguished instrumental behavior (R1) recovers when a behavior that replaced it (R2) is also extinguished. The phenomenon may be relevant to understanding relapse that can occur after the termination of “contingency management” treatments, in which unwanted behavior (e.g., substance abuse) is reduced by reinforcing alternative behavior. When reinforcement is discontinued, the unwanted behavior might resurge. However, unlike most resurgence experiments, contingency management treatments also introduce a negative contingency in which reinforcers are not delivered unless the client has abstained from the unwanted behavior. Two experiments with rats therefore examined the effects of adding a negative “abstinence” contingency to the resurgence design. During response elimination, R2 was not reinforced unless R1 had not been emitted for a minimum period of time (45, 90, or 135 s). In both experiments, adding such a contingency to simple R1 extinction reduced, but did not eliminate, resurgence. Experiment 2 found the same effect in a yoked group that could earn reinforcers for R2 at the same points in time, but without the requirement to abstain from R1. Thus, the negative contingency per se did not contribute. Results suggest that the contingency reduced resurgence by making reinforcers more difficult to earn and more widely spaced in time. This could have allowed the animal to learn that R1 was extinguished in the “context” of infrequent reinforcement—a context more like that of resurgence testing. The results are thus consistent with a contextual (renewal) account of resurgence. The method might provide a better model of relapse after termination of a contingency management treatment.

Extinguished operant behavior can return or "resurge" when a response that has replaced it is also extinguished. Typically studied in nonhuman animals, the resurgence effect may provide insight into relapse that is seen when reinforcement is discontinued following human contingency management (CM) and functional communication training (FCT) treatments, which both involve reinforcing alternative behaviors to reduce behavioral excess. Although the variables that affect resurgence have been studied for some time, the mechanisms through which they promote relapse are still debated. We discuss three explanations of resurgence (response prevention, an extension of behavioral momentum theory, and an account emphasizing context change) as well as studies that evaluate them. Several new findings from our laboratory concerning the effects of different temporal distributions of the reinforcer during response elimination and the effects of manipulating qualitative features of the reinforcer pose a particular challenge to the momentumbased model. Overall, the results are consistent with a contextual account of resurgence, which emphasizes that reinforcers presented during response elimination have a discriminative role controlling behavioral inhibition. Changing the "reinforcer context" at the start of testing produces relapse if the organism has not learned to suppress its responding under conditions similar to the ones that prevail during testing.Operant behavior has been an important focus of laboratory research for many decades because it provides a model for studying the variables that control voluntary behavior. In a typical study of operant behavior, animals such as rats learn to perform a response (e.g., a lever press or chain pull) to receive an outcome (such as a food reinforcer). Although the animal is free to do whatever it "wants" during a session, it can be shown that the rate of its behavior is lawfully related to its consequences. Indeed, once the response has been acquired, it can be reduced through a process known as extinction, in which the reinforcer or outcome is no longer produced by that response. Extinction is a well-known and popular method for reducing behavioral excesses. However, behavior that has been reduced through extinction is prone to recovery and relapse (see , for one review). Therefore, the suppression of operant responding that occurs when reinforcers are omitted should not be taken as evidence that the original learning has been erased or unlearned.

Three experiments examined the role of context in punishment learning. In Experiment 1, rats were trained to lever press for food in Context A and then punished for responding in Context B (by presenting response-contingent footshock). Punishment led to complete suppression of the response. However, when responding was tested (in extinction) in Contexts A and B, a strong renewal of responding occurred in Context A. In Experiment 2, renewal also occurred when initial reinforcement occurred in Context A, punishment occurred in Context B, and testing occurred in a new context (Context C). In both experiments, behavioral suppression and renewal were not observed in groups that received noncontingent (yoked) footshocks in Context B. In Experiment 3, two responses (lever press and chain pull) were separately reinforced in Contexts A and B and then punished in the opposite context. Although the procedure equated the contexts on their association with reinforcement and punishment, renewal of each response was observed when it was tested in its non-punished context. The contexts also influenced response choice. Overall, the results suggest that punishment is specific to the context in which it is learned, and establish that its context-specificity does not depend on a simple association between the context and shock. Like extinction, punishment may involve learning to inhibit a specific response in a specific context. Implications for theories of punishment and for understanding the cessation of problematic operant behavior (e.g., drug abuse) are discussed.

Even when a diet has been successful, people often return to overeating when the diet ends. One potential reason is that behavioral inhibition learned while dieting might not transfer readily outside the context in which it is learned: Basic research indicates that after a behavior is inhibited, a return to the conditioning context or simple removal from the treatment context can cause it to relapse or return (“renewal”). Can hunger and satiety states play the role of context? In two experiments, rats learned a food-seeking response for sucrose or sweet-fatty food pellets while satiated. Responding was then inhibited (extinguished) while they were hungry. On return to the satiated state, food-seeking was renewed. Additional results suggest that associations with hunger/satiety stimuli were learned more readily than those with other potentially useful exteroceptive stimuli. The findings have implications for understanding the role of interoceptive contexts in controlling the inhibition of motivated behavior.

Iptakalim is an ATP-sensitive potassium channel opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Pretreatment with iptakalim diminishes nicotine-induced dopamine (DA) and glutamate release in the nucleus accumbens. This neuropharmacological profile suggests that iptakalim may be useful for treatment of nicotine dependence. Thus, we examined the effects of iptakalim in two preclinical models. First, the impact of iptakalim on the interoceptive stimulus effect of nicotine was evaluated by training rats in a discriminated goal-tracking task that included intermixed nicotine (0.4 mg/kg, SC) and saline sessions. Sucrose was intermittently presented in a response-independent manner only on nicotine sessions. On intervening test days, rats were pretreated with iptakalim (10, 30, 60 mg/kg, IP). Results revealed that iptakalim attenuated nicotine-evoked responding controlled by the nicotine stimulus in a dose-dependent manner. In a separate study, the impact of iptakalim on the reinforcing effects of nicotine was investigated by training rats to lever-press to self-administer nicotine (0.03 mg/kg/infusion). Results revealed that pretreatment with iptakalim (1, 3, 6 mg/kg, IV) decreased nicotine intake (i.e., less active lever responding). Neither behavioral effect was due to a non-specific motor effect of iptakalim, nor to an ability of iptakalim to inhibit DA transporter (DAT) or serotonin transporter (SERT) function. Together, these finding support the notion that iptakalim may be an effective pharmacotherapy for increasing smoking cessation and better understanding its action could contribute medication development.

The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.DOI: http://dx.doi.org/10.7554/eLife.22467.001