Dopamine has profound effects in the mammalian neostriatum. Changes in dopaminergic transmission are key to several movement disorders. In particular, loss of dopaminergic innervation from the substantia nigra pars compacta is central to the pathogenesis of Parkinson's Disease. As such, the receptors mediating dopamine effects are important targets for drug therapies. Recently, a diverse group of genetically distinct dopamine receptor subtypes has been identified, revealing greater diversity than had been anticipated from pharmacological studies. The D1 and D2 receptor protein subtypes have been localized to the striatum using subtype-specific antibodies. It is postulated that the receptor proteins are expressed in discrete neuronal populations in neostriatum and transported to specific pre- and postsynaptic sites where individually they may be responsible for different transmitter and drug effects. The following proposed research will use immunocytochemistry and neuro- anatomical tracing methods to advance our understanding of the molecular pharmacology and synaptic organization of the neostriatum. This will facilitate the logical development of more specific and effective drugs, aimed at those molecular targets, for the treatment of Parkinson's Disease and other disorders of the basal ganglia.
