Cocaine abuse is a significant public health problem for which effective treatments are sought. Cocaine self-administration by nonhumans has been considered a preclinical model of cocaine abuse, and studies of such behavior are thought to have relevance for the analysis and treatment of this disorder. Those interventions that are found to decrease cocaine self-administration in preclinical models may have implications for the development of effective treatments for cocaine abuse. Indeed, preclinical methods of reducing cocaine self-administration have been fruitfully applied to the treatment of cocaine abuse in humans. Recently, it has been asserted that animal models of drug abuse should be developed to more closely approximate clinical treatment conditions (Hughes & Bickel, 1997). Thus, one objective of this proposal is to extend the preclinical methodology of alternative nondrug reinforcement to approximate clinical applications of this approach. Proposed herein are free-operant procedures designed to examine the possibility of reinforcing abstinence from cocaine self-administration in rats using a differential-reinforcement- of-other-behavior (DRO) schedule. This assay will allow examining whether reinforcing pauses in cocaine-maintained responding (abstinence) with an alternative nondrug reinforcer can reduce cocaine self-administration in rats. Parameters of the DRO schedule and the FR schedule of cocaine delivery as well as the unit dose of cocaine will be systematically varied to determine the conditions under which DRO contingencies can attenuate cocaine self-administration in rats. A second objective of this proposal is to examine the separate and combined effects of DA agonist treatment and reinforcing abstinence with a DRO schedule of alternative reinforcement. This experimental approach to reducing cocaine self-administration may provide insights into the variables controlling cocaine self-administration and suggest novel approaches to the treatment of cocaine abuse.
