RT Journal Article SR Electronic T1 Evidence That 5-HT2A Receptors in the Hypothalamic Paraventricular Nucleus Mediate Neuroendocrine Responses to (−)DOI JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 9635 OP 9642 DO 10.1523/JNEUROSCI.22-21-09635.2002 VO 22 IS 21 A1 Yahong Zhang A1 Katerina J. Damjanoska A1 Gonzalo A. Carrasco A1 Bertalan Dudas A1 Deborah N. D'Souza A1 Julie Tetzlaff A1 Francisca Garcia A1 Nicole R. Sullivan Hanley A1 Kumar Scripathirathan A1 Brett R. Petersen A1 Thackery S. Gray A1 George Battaglia A1 Nancy A. Muma A1 Louis D. Van de Kar YR 2002 UL http://www.jneurosci.org/content/22/21/9635.abstract AB 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/2Creceptor agonist (−)DOI [(−)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The 5-HT2A receptor antagonist MDL100,907 ((±)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-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-HT2Creceptor 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.