The effects of adolescent methylphenidate self-administration on responding for a conditioned reward, amphetamine-induced locomotor activity, and neuronal activation

Abstract

Abuse of methylphenidate (Ritalin) is rising, particularly during adolescence and early adulthood, but the long-term effects of its abuse during adolescence are unclear. In experiment 1, we examined the effect of adolescent methylphenidate self-administration (0.0625 mg/infusion), as compared with cocaine self-administration (0.125 mg/infusion), under a fixed ratio 1 schedule of reinforcement in male Sprague-Dawley rats during adolescence (postnatal day (PND) 32-47) on adult dopamine-mediated behaviors (PND >70). These included responding for a conditioned reward (CR), a measure of incentive motivation, and amphetamine-induced locomotor activity. In experiment 2, we aimed to replicate and enhance the effects observed in experiment 1, and we also examined the effects of methylphenidate self-administration during adolescence on adult amphetamine-induced zif268 messenger ribonucleic acid (mRNA) expression. Adolescent rats self-administered both cocaine and methylphenidate. There was no effect of adolescent drug self-administration on adult baseline or amphetamine-induced responding for a CR. However, both adolescent methylphenidate and cocaine self-administration increased amphetamine-induced locomotion. Adolescent methylphenidate self-administration also enhanced amphetamine-induced zif268 mRNA expression in the nucleus accumbens. Our findings suggest that repeated, behaviorally contingent exposure to methylphenidate during adolescence enhances responsivity to the locomotor-stimulating and neuronal activating effects of amphetamine but not incentive motivation.