Faculty Collaboration Database

Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOI. J Neurosci 2002 Nov 01;22(21):9635-42

Date

11/06/2002

Pubmed ID

12417689

Pubmed Central ID

PMC6758011

DOI

10.1523/JNEUROSCI.22-21-09635.2002

Scopus ID

2-s2.0-0036827036 (requires institutional sign-in at Scopus site)   84 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 ((+/-)-alpha(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.

Author List

Zhang Y, Damjanoska KJ, Carrasco GA, Dudas B, D'Souza DN, Tetzlaff J, Garcia F, Hanley NR, Scripathirathan K, Petersen BR, Gray TS, Battaglia G, Muma NA, Van de Kar LD

Author

Julie Tetzlaff PhD Associate Dean, Associate Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenocorticotropic Hormone
Amphetamines
Animals
Corticosterone
Dose-Response Relationship, Drug
Fluorobenzenes
Immunohistochemistry
Male
Microinjections
Neurosecretory Systems
Oxytocin
Paraventricular Hypothalamic Nucleus
Piperidines
Prolactin
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT2A
Receptors, Serotonin
Renin
Serotonin Antagonists
Serotonin Receptor Agonists