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The Journal of Neuroscience, November 1, 2002, 22(21):9635-9642
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, and
Louis D.
Van de Kar
Center for Serotonin Disorders Research and Department of
Pharmacology, Loyola University of Chicago, Stritch School of Medicine,
Maywood, Illinois 60153
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
((±)- -(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-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.
Key words:
serotonin; ACTH; oxytocin; MDL100,907; PVN; prolactin; renin; corticosterone
Copyright © 2002 Society for Neuroscience 0270-6474/02/22219635-08$05.00/0
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