THE DOPAMINE TRANSPORTER - A CRUCIAL COMPONENT REGULATING DOPAMINE TRANSMISSION

The dopamine system is implicated in the control of locomotion, cognit ion, and endocrine function. The relative contribution of the various dopamine-related components is not well established mainly because dru gs that target the dopaminergic system often lack selectivity. The in vivo gene inactivation procedure, or knockout, enables the creation of new strains of mice lacking a specific gene. This technique has been applied recently to inactivate the expression of the plasma membrane d opamine transporter. Here we summarize the main findings obtained with these transgenic mice carrying this ''genetic defect,'' leading to a better understanding of the relative contribution of the dopamine tran sporter regarding locomotor activity, regulation of the expression of peptides under the control of dopaminergic activity, and responses to various drugs targeting the dopamine system, Our results establish not only the central importance of the transporter as the key element con trolling-dopamine levels in the brain, but also its role as an obligat ory target for the behavioral and biochemical action of amphetamine an d cocaine. In addition, the genetically altered mice offer a unique mo del to test the specificity and selectivity of dopamine transporter-ac ting drugs and may provide important new concepts related to the clini cal and social implications of conditions such as Parkinson's disease, schizophrenia, and drug addiction.