Evidence exists to suggest that autoreceptors are present on certain dopamine neurons in the CNS which function to regulate the synthesis and release of this neurotransmitter. Experiments have been designed to pharmacologically characterized the autoreceptor in different anatomical pathways to determine if DA autoreceptors share the same properties in different parts of the brain. This will be done by determining the relative potency of a series of DA agonists and antagonists (neuroleptics) to modify the synthesis of DA in synaptosomes obtained from different brain areas including striatum, nucleus accumbens, olfactory tubercle, frontal cortex, and medial basal hypothalamus. Additional experiments will be carried out to pharmacologically characterize the postsynaptic DA receptors in different anatomical areas of the CNS. This will be done by determining the relative potency of a series of DA agonists and antagonists to modify the DA-sensitive adenylate cyclase or the secretion of prolactin. These studies will determine if DA autoreceptors and postsynaptic-receptors are pharmacologically similar or dissimilar. Autoreceptors will be further characterized by determining if they develop supersensitivity or subsensitivity. Experiments will be conducted to determine if autoreceptors can be demonstrated in intact preparations by studying the effect of drugs on tyrosine hydroxylase activity in the rat after stereotaxic administration or the release of DA from the cat using a push-pull cannula. These studies will provide a better understanding of the physiological and pharmacological control of the synthesis and release of dopamine from central neurons.