Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOI

Yahong Zhang, Katerina J. Damjanoska, Gonzalo A. Carrasco, Bertalan Dudas, Deborah N. D'Souza, Julie Tetzlaff, Francisca Garcia, Nicole R. Sullivan Hanley, Kumar Scripathirathan, Brett R. Petersen, Thackery S. Gray, George Battaglia, Nancy A. Muma, Louis D. Van de Kar

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70 Scopus citations

Abstract

The present study determined whether the serotonin2A (5-HT2A) receptors in the hypothalamic paraventricular nucleus mediate the neuroendocrine responses to a peripheral injection of the 5-HT2A/2C receptor agonist (-)DOI [(-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The 5-HT2A receptor antagonist MDL100,907 ((±)-α-(2,3-dimethoxyphenyl)-1-[2- (4-fluorophenyl-ethyl)]-4-piperidinemethanol), the 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl] carbamoyl]-indoline), or vehicle were microinjected bilaterally through a chronically implanted double-barreled cannula into the hypothalamic paraventricular nucleus 15 min before a peripheral injection of (-)DOI in conscious rats. (-)DOI significantly elevated plasma levels of oxytocin, prolactin, ACTH, corticosterone, and renin. Neither the 5-HT2A receptor antagonist nor the 5-HT2C receptor antagonist, injected alone, altered the basal levels of these hormones. MDL100,907 (0.748, 7.48, and 18.7 nmol) dose dependently inhibited the (-)DOI-induced increase in all of the hormones except corticosterone. In contrast, SB-242084 (10 nmol) did not inhibit (-)DOI-increased hormone levels. To confirm the presence of 5-HT2A receptors in the hypothalamic paraventricular nucleus, 5-HT2A receptors were mapped using immunohistochemistry. Densely labeled magnocellular neurons were observed throughout the anterior and posterior magnocellular subdivisions of the hypothalamic paraventricular nucleus. Moderately to densely labeled cells were also observed in parvicellular regions. Thus, it is likely that 5-HT2A receptors are present on neuroendocrine cells in the hypothalamic paraventricular nucleus. These data provide the first direct evidence that neuroendocrine responses to a peripheral injection of (-)DOI are predominantly mediated by activation of 5-HT2A receptors in the hypothalamic paraventricular nucleus.

Original languageEnglish (US)
Pages (from-to)9635-9642
Number of pages8
JournalJournal of Neuroscience
Volume22
Issue number21
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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