Intermittent methylphenidate during adolescent development produces locomotor hyperactivity and an enhanced response to cocaine compared to continuous treatment in rats

The consequences of chronic methylphenidate (MPH) administration in adolescents for the treatment of attention-deficit/hyperactivity disorder (ADHD) remain to be fully understood. Studies in rats indicate that the pharmacokinetics of psychostimulant administration can powerfully influence the behavioral and neural consequences of chronic treatment. The purpose of the present study was to assess the effects of intermittent (0.8 or 1.6 mg/kg, s.c., twice daily) versus continuous (1.6 or 3.2 mg/kg/day via osmotic minipump) MP administration across four weeks of adolescent development in rats. Results indicate that intermittent treatment produced hyperactivity in a novel open field and increased sensitivity to both the reinforcing and locomotor-activating effects of cocaine. In contrast, continuous MPH resulted in a hypoactive response to the novel open field and a reduced sensitivity to both operant and non-contingent cocaine. To the extent that the continuous release condition models the sustained-release formulations utilized in human ADHD treatment, we interpret these data to indicate that sustained-release formulations are less likely to advance a risk of subsequent substance abuse.