Evidence that 5-HT2A Receptors in the Hypothalamic Paraventricular Nucleus Mediate Neuroendocrine Responses to (-)DOI

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Issue Date
2002-11-01Author
Zhang, Yahong
Damjanoska, Katerina J.
Carrasco, Gonzalo A.
Dudas, Bertalan
D'Souza, Deborah N.
Tetzlaff, Julie
Garcia, Francisca
Hanley, Nicole R. Sullivan
Scripathirathan, Kumar
Peterson, Brett R.
Gray, Thackery S.
Battaglia, George
Muma, Nancy A.
Van de Kar, Louis D.
Publisher
Society for Neuroscience
Type
Article
Article Version
Scholarly/refereed, publisher version
Published Version
http://www.jneurosci.org/content/22/21/9635Metadata
Show full item recordAbstract
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.
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This is the publisher's version, also available electronically from "http://www.jneurosci.org".
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- Pharmacy Scholarly Works [293]
Citation
Zhang, Y., Damjanoska, K. J., Carrasco, G. A., Dudas, B., et al. (2002) Evidence that 5-HT2A Receptors in the Hypothalamic Paraventricular Nucleus Mediate Neuroendocrine Responses to (-)DOI. Journal of Neuroscience, 22(21), 9635-9642.
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