Neurons in the ventral tegmental area are major constituents of central brain pathways of drug reinforcement. Despite this potential central role in the actions of many abused drugs, however, the detailed expression of important neurotransmission genes in these neurons has not been elucidated. The expression of the genes encoding two of the dopamine-cotransmitter peptides, cholecystokinin and neurotensin, have thus been mapped to neurons in this area during this year. In these studies, a surprising region-to-region variation in the expression of neurotensin and CCK genes in these neuronal subdivisions has been found. Such detailed studies are necessary before defining activities of cocaine and other abused drugs on this expression. These approaches thus allow detailed examination of the ways in which drugs and other physiologic processes influence gene regulatory mechanisms that could serve as a store for some of the information about prior drug use that may accompany tolerance and dependence. The potential function of these neurons in human drug-induced reinforcement/reward is being studied as well. Parkinson's disease patients, whose brains lose VTA neurons, are assessed after administration of methylphenidate. Blunting of drug effects on mood in these patients would support a central role for these neurons in reinforcement/reward in man.
