Cocaine self-administration increases the incentive motivational properties of the drug in rats

A progressive increase in the frequency and intensity of drug use is one of the major behavioural phenomena characterizing the development of addictio n. The nature of the drug-induced adaptations involved in this escalating d rug intake remains unknown. Some theories propose that this escalation is d ue to a progressive decrease (tolerance) in the reinforcing or incentive ef fects of the drug. Alternative views posit that with chronic use the reinfo rcing or incentive effects of drugs increase, by a sensitization or a learn ing mechanism. In this report, we address the question of whether escalatin g cocaine intake is paralleled by an increase or a decrease in the reinforc ing and incentive effects of the drug. Using the experimental model of intr avenous drug self-administration with a within-session dose-response paradi gm, we first studied the course of cocaine intake over 14 sessions in rats. After acquisition of cocaine self-administration, cocaine intake progressi vely increased at each dose tested. Then rats, previously allowed to self-a dminister cocaine during either six or 29 sessions, were compared in three different tests of the incentive and reinforcing effects of cocaine: cocain e-induced reinstatement of self-administration, cocaine-induced runway and cocaine-induced place conditioning. As compared with rats briefly exposed t o cocaine self-administration (six sessions), rats with the longer experien ce (29 sessions) exhibited a higher intake of cocaine paralleled by a highe r responsiveness in the cocaine-induced reinstatement and runway tests. Bot h groups of rats were similarly sensitive to the rewarding effects of the d rug as evaluated by the threshold dose of cocaine inducing place conditioni ng. Our results demonstrate that escalating cocaine intake is paralleled by an increase in the motivational properties of the drug in the absence of a pparent signs of tolerance to the reinforcing or incentive effects of cocai ne.