Factors that determine a propensity for cocaine-seeking behavior during abstinence in rats

Individual differences in locomotor responses to novelty and psychostimulants, and sensitization to the reinforcing effects of psychostimulants and are thought to underlie vulnerablity to drug addiction. This study tested whether these factors determine another core feature of drug addiction, the propensity for drug-seeking behavior during abstinence in rats with prior cocaine-self-administration experience. Low and high response groups for each of these factors were determined in outbred rats by the median locomotor response to novelty and amphetamine prior to cocaine self-administration (pre-test), and to amphetamine during abstinence (post-test). Cocaine-seeking behavior during abstinence was measured by the level of drug-paired lever responding during extinction, and also during reinstatement induced by cocaine-associated cues, an amphetamine priming injection, and footshock stress. Animals with low and high locomotor responses to novelty and the amphetamine pre-test showed similar levels of cocaine-seeking behavior during extinction and reinstatement testing. Locomotor responses to amphetamine following cocaine self-administration (post- test) also failed to reinstate cocaine-seeking behavior. Conversely, high levels of amphetamine-induced reinstatement were associated specifically with escalating cocaine intake during prior self-administration. These animals also developed locomotor sensitization to amphetamine following cocaine self-administration (post-test vs. pre-test), but the capacity to develop locomotor sensitization was not sufficient to determine a propensity for cocaine-seeking behavior. The findings suggest that the relationship between locomotor responses to novelty amphetamine and behavioral sensitization a,nd the propensity for cocaine-seeking behavior during abstinence is complex, while the level of drug intake during prior self-administration is a primary determinant of this behavior. (C) 2000 American College of Neuropsychopharmcology. Published by Elsevier Science Inc.