The main objectives of this project are to determine the roles of catecholamines and their receptors in brain functions that regulate motor activity, neuroendocrine secretion, and autonomic function. Levels of monoamines and their metabolites in extracellular fluid in specific brain regions are monitored using in vivo microdialysis. Microdialysis probes with an attached infusion microcannulae provides a means for introducing drugs or isotopically-labeled compounds in the region of the microdialysis probe. The magnitude of release of NE and its metabolites in different nuclei within the hypothalamus is related to the degree of responses of the peripheral sympatho-adrenal medullary system and pituitary adrenocortical axis. In the hypothalamus, immobilization-induced increments in local release of norepinephrine are increased by systemic administration of yohimbine, an alpha2-adrenergic receptor blocking agent. In the striatum, we estimate the rate of dopamine release, reuptake and metabolism by combining microdialysis and tracer kinetics of[3H]-DA and using isotope dilution techniques similar to those being used in the plasma. In rats treated intracerebroventricularly with 6-hydroxydopamine the specific activity of recovered [3H]-DA is similar to that in the perfusate, whereas intact animals that had a specific activity was reduced about 100-fold. Simultaneously obtained values for the specific activities of [3H]dihydroxyphenylacetic acid ([3H]-DOPAC) and [3H]-homovanillic acid were about one-tenth of DA indicating that DA is largely deaminated within the neurons prior to release. The nucleus of the solitary tract (NTS), in the mediodorsal medulla of the brainstem, constitutes the main site of termination of afferents from arterial baroreceptors. In a study of single unit firing of NTS neurons in anesthetized rabbits, we found that most NTS neurons increase their firing rate after i.v. injection of phenylephrine, which increases blood pressure acutely by stimulating alpha1-adrenoceptors on vascular smooth muscle cells. In contrast, electrical stimulation of the PVN usually decreased NTS firing and attenuated or prevented phenylephrine-induced increases in NTS firing. The results support a model for acute resetting of the baroreflex during emotional distress.
