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5HT2 receptors mediate the effects of stress on the activity of periventricular hypophysial dopaminergic neurons and the secretion of alpha-melanocyte-stimulating hormone

JL Goudreau, J Manzanares, KJ Lookingland and KE Moore

Department of Pharmacology and Toxicology, Michigan State University, East Lansing.

The roles of 5-hydroxytryptaminergic (5HT) neurons and receptor subtypes in mediating the effects of stress on the activity of periventricular hypophysial dopaminergic (PHDA) neurons and the secretion of alpha-melanocyte-stimulating hormone (alpha MSH) were examined in female rats. Periventricular hypophysial dopaminergic neuronal activity was estimated by measuring concentrations of 3,4- dihydroxyphenylacetic acid in the intermediate lobe of the pituitary. Brief exposure to diethylether followed by 30 min of supine restraint decreased intermediate lobe 3,4-dihydroxyphenylacetic acid concentrations and increased plasma concentrations of alpha MSH. These stress-induced effects were not observed in animals in which 5HT neurons had been previously destroyed by 5,7-dihydroxytryptamine or inhibited by the administration of the 5HT1A receptor agonist 8-hydroxy- 2-(di-n-propyl-amino)-tetralin. Pretreatment of rats with the 5HT2 receptor antagonist MDL-11,939 blocked the inhibitory effects of stress on intermediate lobe 3,4-dihydroxyphenylacetic acid concentrations and the corresponding increase in plasma alpha MSH concentrations, whereas the 5HT3 receptor antagonist ondansetron was without effect. These results reveal that 5HT neurons, acting via 5HT2 receptors, mediate the inhibitory effects of stress on periventricular hypophysial dopaminergic neurons and the consequent increase in secretion of alpha MSH.

Volume 265, Issue 1, pp. 303-307, 04/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1993 by the American Society for Pharmacology and Experimental Therapeutics.