ABSTRACT
Dopamine is one of the major neurotransmitters in the basal ganglia and mesolimbic areas of the brain, and disturbances in dopaminergic activity have been implicated in the pathogenesis of frequently encountered motor and behavioral disorders. In particular, alterations in the density or sensitivity of D2 dopamine receptors have been observed in schizophrenia, tardive dyskinesia, and Parkinson's disease. Tardive dyskinesia and the positive symptoms of schizophrenia appear to be the result of excessive dopaminergic neurotransmission. Continuous infusion of dopaminergic drugs was achieved with subcutaneously implanted Alzet osmotic minipumps. A novel approach to pharmacologically alter the expression of dopamine receptors is the use of antisense oligodeoxynucleotides targeted to the mRNAs encoding the different receptor subtypes. Many of the pharmacologic agents which were believed initially to be highly selective have been shown now to interact with more than one dopamine receptor subtype, thus leading to non-selective effects.
