NEW INSIGHTS INTO DOPAMINERGIC RECEPTOR FUNCTION USING ANTISENSE AND GENETICALLY ALTERED ANIMALS¹

Dopaminergic receptors are widespread throughout the central and peripheral nervous systems, where they regulate a variety of physiological, behavioral, and endocrine functions. These receptors are also clinically important drug targets for the treatment of a number of disorders, such as Parkinson's disease, schizophrenia, and hyperprolactinemia. To date, five different dopamine receptor subtypes have been cloned and characterized. Many of these subtypes are pharmacologically similar, making it difficult to selectively stimulate or block a specific receptor subtype in vivo. Thus, the assignment of various physiological or behavioral functions to specific dopamine receptor subtypes using pharmacological tools is difficult. In view of this, a number of investigators have—in order to elucidate functional roles—begun to use highly selective genetic approaches to alter the expression of individual dopamine receptor subtypes in vivo. This review discusses recent studies involving the use of genetic approaches for the study of dopaminergic receptor function.