5-Hydroxytryptamine2 receptor-mediated regulation of periventricular-hypophysial dopaminergic neuronal activity and the secretion of alpha-melanocyte-stimulating hormone
Goudreau, J.L.; Lookingland, K.J.; Moore, K.E.
Journal of Pharmacology and Experimental Therapeutics 268(1): 175-179
1994
ISSN/ISBN: 0022-3565 PMID: 8301554 Document Number: 430293
The present study examined the effects of the 5-hydroxytryptaminergic (5HT)-2/1c agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on periventricular-hypophysial dopaminergic (DA) neuroneal activity and the secretion of alpha-melanocyte-stimulating hormone (alpha-MSH). For comparison, the effects of DOI on tuberoinfundibular DA neuronal activity and the secretion of prolactin were also examined. Periventricular hypophysial and tuberoinfundibular DA neuronal activities were estimated by measuring the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the terminal regions of these neurons; i.e., in the intermediate lobe of the pituitary and median eminence, respectively. Acute administration of DOI produced dose- and time-related decreases in intermediate lobe DOPAC concentrations and corresponding increases in plasma alpha-MSH concentrations. Pretreatment of animals with either the 5HT-2/1c antagonist ritanserin or the selective 5HT-2 antagonist alpha-phenyl-1-2-phenylethyly 4-piperidine methanol (MDL-11,939) blocked the DOI-induced decrease in intermediate lobe DOPAC concentrations and increase in plasma alpha-MSH concentrations. Acute administration of DOI produced dose- and time-related increases in plasma prolactin concentrations but did not alter DOPAC concentrations in the median eminence. Furthermore, the DOI-induced increase in plasma prolactin concentrations was blocked by ritanserin, but not MDL-11,939 pretreatment. Taken together, these data suggest that DOI inhibits periventricular hypophysial DA neuronal activity and increases the secretion of alpha-MSH by activating 5HT-2 receptors, whereas the DOI-induced prolactin secretion is independent of a decrease in tuberoinfundibular DA neuronal activity and is most likely mediated by 5HT-2/1c receptor activation.