Cocaine withdrawal alters regulatory elements of dopamine neurons.

Cocaine is an extremely reinforcing drug that is readily selfadministered by both animals and humans. Although cocaine affects many transmitter systems in the brain, the best characterized are the dopaminergic neurons that originate in the midbrain and innervate areas in the forebrain. These include the nigrostriatal, mesolimbic, and mesocortical dopaminergic systems. Adequate characterization of these systems includes not only cocaine’s acute effects and the effects of long-term exposure but also the functional, biochemical, and neuronal changes after its long-term withdrawal. The reinforcing effects of cocaine have been linked to its ability to block dopamine uptake (Kuhar et al. 1991; Ritz et al. 1987), particularly at the nucleus accumbens (Koob 1992; Woolverton and Johnson 1992). The focus of the work described below is the changes that emerge in the regulatory elements of dopamine neurons after repeated cocaine administration and its withdrawal.