The long-term objective of this project is to characterize the regulation of different dopaminergic neuronal systems in the rat brain. The hypothesis that will be tested is that anatomically distinct dopaminergic neuronal systems in the brain subserve different function and, in turn, are differentially regulated by afferent neuronal and/or endocrinological systems. Elucidation of these regulatory mechanisms should assist in the development of drugs that can selectively modulate the activity of specific dopaminergic neurons; such drugs should have therapeutic utility in treating neurological, psychiatric and endocrinological disorders. The characteristics of """"""""classical"""""""" nigrostriatal dopaminergic neurons will be compared with little-studied hypothalamic dopaminergic neurons that comprise the tuberohypophysial and incertohypothalamic systems. The activities of these neurons will be estimated neurochemcially by measuring rates of synthesis, turnover and metabolism of dopamine in brain regions that contain perikarya and terminals of these neurons. Studies on tuberohypophysial dopaminergic neurons will focus on the inhibitory actions of these neurons on the secretion of pro-opiomelanocortin-derived peptides (primarily alphaMSH) from the intermediate lobe of the pituitary gland. The ability of stressful stimuli and a variety of pharmacological and endocrinological manipulations know to alter putative neurotransmitter systems will be examined for their ability to alter tuberohypophysial dopaminergic neuronal activity and circulating level of alphaMSH. After validating neurochemical methods, appropriate techniques will be selected to evaluate the effect of afferent neuronal projections and the hormonal milieu on the activity of incertohypothalamic dopaminergic neurons. Focus of these studies will be on the ability of pituitary (prolactin, luteinizing hormone) and gonadal (testosterone, estrogen) hormones to modulated the activity of incertohypothalamic dopaminergic neurons in intact and castrated male and female rats.
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