Drug addiction is a serious health issue. The reported relationship between ADHD diagnosis and increased substance abuse is obscured by lacking uniformity in diagnosis of ADHD, and long-term exposure to stimulants in those who are treated. Some individuals receiving medication may not have a distinct clinical disorder and may be more reactive to methylphenidate (MP) (the most widely prescribed treatment). In animal models, enhanced reactivity (sensitization) to stimulants can be measured as increased motor activity or propensity to self-administer abused drugs. Individuals at greater risk for acquiring self- administration (SA) can be predicted based on drug-independent criteria; their locomotor response to a novel setting. These individuals, high responders (HR), are more readily sensitized following drug exposure and are known to show basal and drug-induced differences in DA neurotransmission. The general aim of this study is to determine whether MP is a psychostimulant that causes behavioral sensitization following repeated exposure. Measuring MPs locomotor stimulant effect and ability to increase acquisition of cocaine SA will test this. We will determine whether there are subgroups of animals (HR) that are more susceptible to these effects. Using extracellular single-unit recording and microiontophoretic techniques we will measure post-synaptic (receptor function in the nucleus accumbens (Nac)) effects in a circuit known to mediate both the rewarding and motor stimulant effects of other indirect DA agonists. We will test before and after repeated MP in order to determine basal from drug-induced changes and compare them to neuronal adaptations that are known to occur following repeated exposure to amphetamine and cocaine.
