Rapid and persistent sensitization to the reinforcing effects of cocaine

The development of drug addiction involves a transition from recreational use to compulsive drug seeking and taking, and this progression can occur rapidly with cocaine use. These data highlight the importance of early drug exposure and the development of drug dependence; however, little experimental attention has been paid to this phenomenon in animal models of drug abuse. The present experiments demonstrate a progressive and rapid sensitization to the reinforcing strength of cocaine assessed using a progressive ratio (PR) schedule in rats. The first experiment found that rats show increased breakpoints over a 2-week period following acquisition. Subsequent experiments examined the role of total cocaine intake during the initial exposure period and found that low intakes (20 mg/kg/day x 5 days) resulted in sensitization, whereas relatively higher intake (60 or 100 mg/kg/day x 5 days) suppressed the development of sensitization. In contrast, this higher level of intake (60 mg/kg/day x 5 days) only transiently suppressed the expression of sensitization. Examination of breakpoints maintained by various doses of cocaine revealed an upward and leftward displacement of the cocaine dose-effect curve, relative to nonsensitized animals. These studies describe a form of sensitization that occurs rapidly to the reinforcing effects of cocaine, and provide a model to study the potential impact of initial experience on the development of drug dependence.