Only by understanding behavioral and neurobiological mechanisms that underlie relapse can we reduce the high prevalence of relapse to drug addiction. To study these mechanisms, the reinstatement model of relapse has been developed, where animals learn to self-administer a drug, and then responding for the drug is suppressed by extinction: responses no longer provide access to the drug. Once responding is suppressed, exposure to the drug, drug-associated stimuli, or stimuli signaling drug availability result in a resumption of responding for the drug, despite its continuing absence. These same conditions promote relapse in recovering addicts. Also, inactivating brain regions that are active during self-reported craving reduce reinstatement behavior. However, in humans, abstinence is rarely forced;addicts choose to reduce or stop drug use, replacing maladaptive drug use with other, adaptive behaviors. Additionally, in the animal model, increasing the period of forced abstinence increases subsequent reinstatement;yet in humans longer periods of abstinence reduce the likelihood of relapse. Thus there could be a fundamental difference in the behavioral and neurobiological mechanisms that underlie drug self-administration behavior that has been suppressed by extinction verses behavior suppressed by reinforcing an alternative behavior. In this proposal, (1) conditions are established that result in ethanol-predominant or ethanol-suppressed choices under a concurrent fixed-ratio schedule of food and ethanol reinforcement. Then, reinstatement of extinction-suppressed or choice-suppressed responding is compared following several treatments known to reinstate extinction-suppressed responding and precipitate relapse. (2) The impact of reversible inactivation of several brain regions on reinstatement responding under extinction-suppressed and choice-suppressed responding is compared. (3) The impact of the length of the period of response suppression on reinstatement responding in each procedure is determined. Finally, (4) stimulus generalization curves are established following 30 or 60 days of ethanol self-administration or suppressed ethanol-self-administration under both procedures. This method provides information about the stimulus control of a behavior and could help us understand conditions that increase vulnerability to relapse or promote recovery. These studies will begin to build an integrative relationship between studies on the determinates of choice and reinstatement behaviors.
This project enhances a commonly used animal model of relapse behavior by suppressing drug taking by reinforcing an alternative behavior rather than removing drug altogether. This is more similar to the decisions required of recovering addicts. The influence of brain regions and abstinence period will be tested.
