Animal models of relapse to drug seeking have focused primarily on relapse induced by exposure to drugs, drug-associated cues or contexts, and foot-shock stress. However, relapse in human drug abusers is often precipitated by loss of alternative non-drug reinforcement. The present experiment used a novel “resurgence” paradigm to examine relapse to cocaine seeking of rats as a result of loss of an alternative source of non-drug reinforcement. Rats were first trained to press a lever for intravenous infusions of cocaine. Next, cocaine deliveries were omitted and food pellets were provided for an alternative nose-poke response. Once cocaine seeking was reduced to low levels, food pellets for the alternative response were also omitted. Cocaine seeking increased with the loss of the alternative non-drug reinforcer (i.e., resurgence occurred) despite continued extinction conditions. The increase in cocaine seeking did not occur in another group of rats injected with SCH 23390 prior to the loss of the alternative reinforcer. These results suggest that removal of an alternative source of reinforcement may induce relapse of cocaine seeking and that the dopamine D1 receptor may play a role in this effect.

Persistent drug seeking is a defining property of substance abuse and is generally thought to depend, in part, on exposure to drug-associated contexts. Behavioral momentum theory provides a set of methods and a theoretical framework for understanding how stimulus contexts contribute to the persistence of operant behavior. Earlier research has extended behavioral momentum theory to alcohol self-administration, but not to intravenous drug self-administration. This experiment extended behavioral momentum theory to cocaine self-administration by examining the effects of frequency of cocaine reinforcement in a context on resistance to extinction. Rats self-administered 0.32 mg/kg infusions of cocaine in a multiple schedule of reinforcement arranging two distinct contexts. Responding in a Rich context was reinforced by cocaine infusions at a higher frequency (i.e. variable interval 120 s) and in a Lean context at a lower frequency (variable interval 360 s). After establishment of responding in the two contexts, resistance to extinction was examined. Preextinction response rates for cocaine were similar in the Rich and Lean contexts. Nonetheless, relative resistance to extinction was greater in the Rich context than in the Lean context. The difference in resistance to extinction in the two contexts was well described by a quantitative model of behavioral momentum. These results suggest that the frequency of drug reinforcement in a context contributes to the persistence of drug seeking in that context, and that behavioral momentum theory might be useful for understanding how drug-associated contexts contribute to the persistence of drug seeking.

Rationale Repeated nicotine exposure causes neuroadaptations in limbic cortico-striatal circuits involved in learning and motivation. Such alterations are relevant to addiction because they are suggested to mediate the ability of smoking-associated stimuli to control behavior and to enhance nicotine-seeking and -taking behaviors. Female smokers report higher cue reactivity relative to their male counter parts, yet little is known about putative gender-specific effects of adolescent nicotine exposure on reward-related learning. Prior repeated nicotine exposure in adult male rats enhances Pavlovian approach behavior and conditioned reinforcement Objective Given that smoking is typically initiated during adolescence, here we assessed the extent to which adolescent nicotine exposure impacts Pavlovian approach and conditioned reinforcement in male and female rats. Methods Rats were injected with nicotine on postnatal days 31–45 prior to training on Pavlovian approach behavior starting on day 51. They were trained to associate a conditioned stimulus (CS), illumination of a magazine light, and tone, with an unconditioned stimulus (US), the delivery of water, for 10-daily sessions, and then were tested on the acquisition of responding with conditioned reinforcement. Results Adolescent nicotine exposure selectively increased approach to the magazine during the CS in males but decreased approach to the magazine during the CS in female rats. Vehicle-exposed female rats, however, showed greater magazine approach during the CS than did male control rats. Prior nicotine exposure also enhanced conditioned reinforcement in both male and female rats. Conclusions Repeated exposure to nicotine during adolescence had opposite effects on Pavlovian approach behavior in male and female rats but produced enhancement of increases in acquisition of a new response with conditioned reinforcement. Novel information on how nicotine exposure influences reward-related learning during adolescence may increase our understanding of neurobiological mechanisms involved in the initiation of smoking behavior.

Although the environmental determinants of context-specific behavioral persistence have been extensively studied within behavioral momentum theory, little is known about the neurobiological determinants. The present experiment assessed the impact of indirect dopamine agonism with D-amphetamine or dopamine D1 receptor antagonism with SCH23390 on context-specific persistence of behavior. Two groups of rats were trained to make operant responses for equal rates of food delivery in two alternating contexts arranged across sessions. Following baseline, rats received either drug (D-amphetamine or SCH23390) or saline injections before each context. Resistance to extinction and reinstatement in each context were subsequently tested in the absence of drug. Previous exposure to D-amphetamine increased resistance to extinction and reinstatement of behavior, whereas SCH23390 had little impact on resistance to extinction and enhanced reinstatement in the saline context. Quantitative analyses based on behavioral momentum theory suggested that previous treatment with D-amphetamine within a stimulus context may have resulted in a shift to more habitual stimulus-driven behavior that was impacted less by reinforcer omission during subsequent extinction. These results suggest that the persistence of behavior is greater in a context associated with dopamine receptor agonism and that the activity at D1 receptors may differentially modulate extinction and reinstatement performance. These findings may serve as a starting point for future examination and integration of the biological and environmental determinants of behavioral persistence within the framework of behavioral momentum theory.