Transient amelioration of the sensitization of cocaine-induced behaviors in rats by the induction of tolerance.

Intermittent administration of cocaine produced a progressive increase in the stereotypy response of rats to a challenge dose of cocaine (7.5 mg/kg, i.p.). Continuous infusion of cocaine (80 mg/kg per day) via osmotic pumps for 7 days into the sensitized rats produced tolerance to the behavioral responses to the challenge dose of cocaine 1 day after the removal of the pumps. Therefore, tolerance can mask the expression of behavioral sensitization in rats. However, by 10 days after the removal of the pumps, the behavioral tolerance was reversed and the rats again displayed a sensitized response to cocaine. Therefore, the tolerance to cocaine was temporary while the underlying sensitization persisted. The development of tolerance did not alter the underlying sensitization demonstrating that these represent independent phenomena. The relationship between sensitization and tolerance observed in these studies may provide a model relevant to the progress in humans of addiction to psychomotor stimulants.