JPET Over 1500 Individual Drug Articles!

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on February 11, 2003; DOI: 10.1124/jpet.102.045120

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jpet.102.045120v1
305/2/541    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gulinello, M.
Right arrow Articles by Smith, S. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gulinello, M.
Right arrow Articles by Smith, S. S.


Received for publication November 8, 2002.
Revised November 26, 2002.
Accepted for publication January 24, 2003.

Anxiogenic Effects of Neurosteroid Exposure - Sex Differences and Altered GABAA-Receptor Pharmacology in Adult Rats

Maria Gulinello 1* Sheryl S. Smith 1

1 SUNY Downstate Medical Center

* Address correspondence to: E-mail: mgulin{at}aecom.yu.edu

Abstract

Acute exposure to progesterone or its neurosteroid derivative allopregnanolone (3{alpha},5{alpha}-THP), is anxiolytic, consistent with the GABA-modulatory effects of 3{alpha},5{alpha}-THP at the GABAA-receptor. However, continuous exposure to progesterone increases anxiety in association with increased expression of the benzodiazepine-insensitive GABAA-receptor {alpha}4 subunit. Furthermore, negative mood symptoms and altered GABAA-receptor pharmacology in patients with premenstrual dysphoric disorder occur in the early luteal phase in association with peak circulating levels of progesterone and 3{alpha},5{alpha}-THP. Because sex differences have been reported in steroid-regulated anxiety responses, the present study investigated the role of sex and development in the regulation of anxiety following short-term exposure to 3{alpha},5{alpha}-THP. To this end, we compared the effects of hormone administration in adult male, adult female and juvenile female rats. Increased anxiety in the elevated plus maze was evident in all groups following 48 hr exposure to either 3{alpha},5{alpha}-THP or progesterone. At this time point, alterations in the anxiolytic profile of benzodiazepine agonists and antagonists were also observed in both adult males and females in the elevated plus maze. However, sex differences in the acoustic startle response (ASR) were observed after short-term hormone treatment such that only female rats displayed the increased ASR indicative of higher anxiety levels. These results suggest that although neurosteroid exposure may influence both the pharmacological properties of the GABAA-receptor and the manifestation of anxiety in both sexes, the effects of neurosteroids may be modulated in a sex and task-specific manner.


Key words: GABA-A Receptor, acoustic startle, allopregnanolone, anxiety, elevated plus maze, progesterone


This article has been cited by other articles:


Home page
 J. Neurosci.Home page
D. J. Toufexis, C. Davis, A. Hammond, and M. Davis
Progesterone Attenuates Corticotropin-Releasing Factor-Enhanced But Not Fear-Potentiated Startle via the Activity of Its Neuroactive Metabolite, Allopregnanolone
J. Neurosci., November 10, 2004; 24(45): 10280 - 10287.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2003 by the American Society for Pharmacology and Experimental Therapeutics.