Opposing Short-Term and Long-Term Effects of Amphetamine Sensitization on Operant Responding for a Food Reinforcer

Abstract

Repeated exposure to drugs of abuse causes behavioral sensitization, a progressive and persistent increase in the psychomotor response to drugs. Behavioral sensitization is accompanied by altered responses to motivational stimuli and a wide array of neuroadaptations in limbic corticostriatal systems. Interestingly, both the behavioral and neural changes show markedly different effects when tested during induction of sensitization or after a period of drug abstinence. To directly compare short- and long-term effects of repeated drug administration on motivational behavior, we assessed performance of an operant conditioning task in rats either following a three week period of abstinence from amphetamine treatment or during the induction of amphetamine sensitization. We observed a biphasic response pattern for reward, in which operant responding was persistently potentiated following abstinence but transiently decreased when animals were tested during induction. We propose that drug-induced changes in the function of reward-related cortico-striatal systems underlie this pattern of sensitization-induced changes in motivated behavior.