This Article Full Text (OnlineFirst PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Scopus Google Scholar Articles by Jiang, X. Articles by Li, H. PubMed PubMed Citation Articles by Jiang, X. Articles by Li, H. Social Bookmarking                         What's this?

5-HT_2A receptor antagonism by MDL 11,939 during inescapable stress prevents subsequent exaggeration of acoustic startle response and reduced body weight in rats

¹ Center for the Study of Traumatic Stress, Department of Psychiatry; Neuroscience Program, Uniformed Services University of the Health
² Center for the Study of Traumatic Stress, Department of Psychiatry
³ A summer student from Wootton High School

^* To whom correspondence should be addressed. E-mail: hli{at}usuhs.mil.

	Abstract

Activation of central 5-HT_2A receptor signaling and its subsequent alterations have been implicated in the pathophysiological response to stress and the pathogenesis of stress-associated psychiatric disorders. To further examine the association between alterations in central 5-HT_2A receptor signaling and the occurrence of stress-induced psychiatric symptoms, the present study, utilizing a learned helplessness stress model in rats, determined whether 5-HT_2A receptor signaling blockade during stress could prevent the occurrence of stress-induced physical and behavioral abnormalities. Rats subjected to restraint/tail shock for three days developed long-lasting elevated acoustic startle response (ASR) and reduced body weight, compared to non-stressed control animals. However, administration of the selective 5-HT_2A receptor antagonist, MDL 11,939 (-phenyl-1-(2-phenylethyl)-4-piperidinemethanol), 30 min prior to exposure of the animals to the stress protocol prevented the subsequent occurrence of elevated ASR and reduced body weight in a dose-dependent manner in stressed subjects. Administration of MDL 11,939 to the animals immediately after exposure to the stress protocol also prevented the occurrence of exaggerated ASR, but was not able to normalize body weight. These findings suggest a critical role of the central 5-HT_2A receptor activation in developing the pathophysiology associated with elevated ASR and reduced body weight during stress. The differential effects of MDL 11,939 on startle response and body weight and its potential clinical significance are discussed.

First published on November 4, 2009
Journal of Psychopharmacology 2009, doi:10.1177/0269881109106911


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?