Pretreatment with methylphenidate sensitizes rats to the reinforcing effects of cocaine

Abstract

Repeated administration of cocaine produces sensitization to its locomotor-activating effects and increases the rate at which cocaine self-administration behavior is acquired. Methylphenidate is administered clinically on a daily basis, predominantly to children and adolescents, for the treatment of attention-deficit hyperactivity disorder (ADHD). It has been demonstrated previously that pretreatment with methylphenidate administered to periadolescent rats decreased the latency to acquisition of cocaine self-administration. Since methylphenidate is often also administered to adults with ADHD, the present study was conducted to determine the effects of prior administration of methylphenidate (5 or 20 mg/kg/day for 9 days) to adult rats on the rate of acquisition for cocaine self-administration (0.25 mg/kg/infusion). The higher dose of methylphenidate significantly decreased the latency for acquisition of this behavior, suggesting that the rats were sensitized to the reinforcing effects of cocaine after treatment with methylphenidate. These findings add to the growing body of evidence suggesting cross-sensitization between the behavioral effects of psychostimulants. Further, insofar as self-administration is a reliable measure of abuse liability, these data suggest that a short-duration pretreatment with a high dose of methylphenidate to adults increases vulnerability to cocaine abuse.