Individual Differences in Dopamine Cell Neuroadaptations Following Cocaine Self-Administration

Abstract

Addictive drugs produce neuroadaptations in dopamine neurons of the ventral tegmental area. It is unknown if individual differences in these neuroadaptive responses can account for naturally occurring differences in drug addiction liability. To study this question, we took advantage of high-responder (HR) and low-responder (LR) rats, a population that exhibits spontaneous differences in several models of addiction. High-responder and LR rats were allowed to self-administer saline or a high dose of cocaine (500 microg/kg/infusion) over a brief period, to normalize drug intake across individuals. Drug-induced changes in the baseline activity of ventral tegmental area dopamine neurons were recorded after various periods of withdrawal. All rats developed self-administration behavior and showed similar levels of drug intake. Withdrawal from cocaine self-administration increased dopamine cell firing and bursting in all animals. However, these changes in firing rates and patterns were more persistent in HR than in LR rats. These results demonstrate individual differences in the duration of drug-induced neuroadaptations in dopamine neurons of the ventral tegmental area. More persistent elevation of dopamine cell activity and reduced capacity to return to baseline levels may be an important factor contributing to the development of addiction in "at-risk" individuals.