Analysis of the role of D2 receptors in methylphenidate-induced conditioned place preference

ADHD is one of the most commonly diagnosed disorders during adolescence. Recently, significant increases in the diagnosis of ADHD have caused the prescription of the ADHD medication methylphenidate (MPH) to increase. MPH is a psychostimulant that blocks the dopamine transporter, which is responsible for dopamine reuptake at the synapse. The blockade of the dopamine transporter results in an increase in the availability of dopamine in the synaptic cleft. This increase of dopamine accounts for the addictive properties of a MPH due to strong effects on portions of the brain’s drug-reward pathway, including the striatum and nucleus accumbens. In this study, we hypothesized that dopamine D2 receptor antagonism would block MPH-induced conditioned place preference. We also hypothesized this will be more effective in adolescent male rats as compared to adolescent female rats based on evidence that has shown a higher density of dopamine D2 receptors in the brain’s reward areas of adolescent male rats. The effects of MPH on the associative effects of MPH was analyzed using the conditioned place preference (CPP) behavioral paradigm. Results showed that MPH-induced CPP was not blocked by the dopamine D2 receptor antagonist, likely due to its effects on the inhibitory presynaptically located dopamine D2 autoreceptor. The importance of these findings is discussed relative to the role of the D2 receptor in MPH addiction.