Effects of Methylphenidate on Conditioned Place Preference in Adolescent Mice Data collection is in progress

Abstract

Methylphenidate (MPH) (e.g., RitalinTM), prescriptions have significantly increased concomitant with increases in ADHD diagnosis and recent concerns of misdiagnosis and abuse. It was demonstrated that adolescent exposure to a low dose of MPH induces behavioral sensitization, which models addiction and neural circuitry involving the output of the Nucleus Accumbens. Some effects were female-specific. Developmental MPH exposures may affect other features of addiction.

The Conditioned Place Preference (CPP) measures drug-induced environmental associations and models the development of drug-related cues. Expression of CPP demonstrates alterations in the output of the Ventral Tegmental Area in the mesocorticolimbic dopamine reward pathway of the brain. Plasticity in these brain areas form a neurobiological basis for addiction.

This study explores the effects of adolescent exposure of low dose (1mg/kg; modeling a prescription dosage) MPH on the development of CPP in both male and female mice versus saline controls. The study utilizes a CPP system (Kinder Scientific), which contains two chambers. Saline and MPH are each paired with a chamber which have distinct environmental stimuli. During post-conditioning, drug-induced preferences are tested. More time spent in the drug-paired chamber operationalizes CPP. Our data demonstrates that a high dose of MPH (10mg/kg) induces CPP in adult male mice. These data support the addictiveness of MPH and validates our model.

Keeping with previous results, we predict that a low dose of MPH, will induce CPP and that this effect will be heightened in female mice. These results have important clinical implications related to ADHD misdiagnosis and MPH over prescription.