Chronic Treatment with Extended Release Methylphenidate Does Not Alter Dopamine Systems or Increase Vulnerability for Cocaine Self-Administration

Methylphenidate (MPH) in a sustained release regimen is tested for long term neurobiological effects and later risk for cocaine use in juvenile nonhuman primates. Juvenile rhesus monkeys were treated daily with extended release MPH or placebo for about one year, with dosing titrated to therapeutic blood levels and adjusted through the study. Dopamine system measures included PET imaging for D2/D3 receptor and dopamine transporter (DAT) availability, along with growth and developmental milestone assessments. The results indicate that chronic MPH did not differentially change growth trajectories or DAT and D2/D3 receptor availability after treatment. After a washout period, D2/D3 availability in MPH treated animals did not decline at the same rate as controls. Cocaine self administration was then evaluated using an IV cocaine reinforcement procedure across a range of doses, and MPH treatment showed no differences in cocaine acquisition rates, overall response rates, or cocaine intake, implying no increased vulnerability to cocaine abuse under these conditions.