The Effects of Clozapine on Methylphenidate-Induced Conditioned Place Preference

Abstract

Methylphenidate, (MPH), is commonly prescribed for attention deficit/hyperactivity disorder (ADHD). It is similar to cocaine in that it inhibits the dopamine transporter to elevate extracellular dopamine levels and has reinforcing effects. As ADHD diagnoses have increased, MPH abuse has increased as well. There is evidence that DA antagonists such as Clozapine may be effective in mitigating cocaine abuse. Therefore, it is hypothesized that Clozapine will inhibit the rewarding effects of MPH in a conditioned place preference (CPP) paradigm. The data showed that both MPH and Clozapine treated groups had a significant aversion to the drug-paired compartment. Because MPH produced a conditioned aversion, the effect of Clozapine on the rewarding effects of MPH remains to be elucidated. Future studies using lower doses of MPH, as well as those analyzing dopamine levels in the striatum and prefrontal cortex would provide evidence of the effect of Clozapine on mesolimbic dopamine systems.