Examination of the role of dopamine D2 and adrenergic α2 receptors in resurgence of food seeking.

Resurgence refers to the reappearance of an extinguished operant behavior when reinforcement for an alternative behavior is also subsequently discontinued. Resurgence has been noted as a source of relapse to problem behavior following interventions involving alternative reinforcement, and has also been recently used as an animal model of relapse to drug seeking induced by reinforcement loss. Existing information about the neuropharmacology of resurgence is scarce, but suggests overlap between relapse observed in the resurgence model and relapse observed in reinstatement and renewal models. In the present experiment rats earned food pellets for pressing a target lever in Phase I. In Phase II lever pressing no longer produced food, but food was delivered for an alterative nose poke response. Finally in Phase III, neither response produced food deliveries. Prior to these Phase III sessions, separate groups of rats were injected with 0, 50, or 100 µg/kg of the dopamine D2 receptor antagonist raclopride or 0, 20, or 40 µg/kg of α 2 agonist clonidine. Both doses of raclopride were effective in blocking resurgence, but there was evidence that the higher dose did so via motor rather than motivational impairment. Only the higher dose of clonidine blocked resurgence, but did so with no evidence of motor impairment. Raclopride significantly impacted extinction of the alternative poke at both doses tested, whereas clonidine had no effect at either dose. The results of the present study provide additional information about the neuropharmacology of resurgence, as well as additional evidence of overlap between resurgence, reinstatement, and renewal.

Loss of nondrug reinforcement in one context produces alcohol seeking in another context.

In the resurgence preparation, extinguished alcohol-maintained responding increases when food reinforcement introduced into the same context during extinction is also subsequently removed. However, drug and nondrug reinforcers may often be obtained in separate specific contexts. Accordingly, we aimed to determine whether extinguished behavior previously maintained by alcohol would increase upon elimination of nondrug reinforcement within a multiple schedule arranging distinct discriminative stimulus contexts of food and alcohol availability. In Experiment 1, rats earned food or alcohol in alternating stimulus contexts within a multiple schedule. First, alcohol-maintained responding was extinguished and then food deliveries in the alternating component were also discontinued. Extinguished alcohol-maintained responding increased upon discontinuation of food deliveries. However, periods of alcohol availability alternated with periods of extinction during a portion of training; thus, elimination of food reinforcers during the resurgence test may have inadvertently served as a cue for alcohol availability. In Experiment 2, the training phase that complicated interpretation of the results of Experiment 1 was eliminated. Alcohol-maintained responding again increased when food-maintained responding was placed on extinction in the other component. The present results indicate that loss of nondrug reinforcement in one discriminative context can increase extinguished alcohol seeking in another context and that multiple schedules of reinforcement might be useful for examining such effects.

Loss of alternative non-drug reinforcement induces relapse of cocaine-seeking in rats: role of dopamine D(1) receptors.

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 (ie, resurgence occurred) despite continued extinction conditions. The increase in cocaine seeking did not occur in another group of rats injected with SCH 23390 before 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 D(1) receptor may have a role in this effect.

Behavioral momentum and relapse of ethanol seeking: nondrug reinforcement in a context increases relative reinstatement.

Drug-related stimuli seem to contribute to the persistence of drug seeking and relapse. Behavioral momentum theory is a framework for understanding how the discriminative-stimulus context in which operant behavior occurs governs the persistence of that behavior. The theory suggests that both resistance to change and relapse are governed by the Pavlovian stimulus-reinforcer relation between a stimulus context and all sources of reinforcement obtained in that context. This experiment examined the role of the Pavlovian stimulus-reinforcer relation in reinstatement of ethanol seeking of rats by including added response-independent nondrug reinforcement in the self-administration context. Although rates of ethanol-maintained responding were lower in a context with added nondrug reinforcement than a context with ethanol alone, relative resistance to extinction and relative reinstatement were greater in the context previously associated with the nondrug reinforcer. Thus, both relative resistance to extinction and relative relapse of ethanol seeking depended on the Pavlovian stimulus-reinforcer relation between a context and all sources of reinforcement in that context. These findings suggest that to understand how drug-related contexts contribute to relapse, it may be necessary to consider not only the history of drug reinforcement in a context, but also the wide variety of other reinforcers obtained in such contexts.