QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.061432v1 309/1/267    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gogos, A. Articles by Van den Buuse, M. Search for Related Content PubMed PubMed Citation Articles by Gogos, A. Articles by Van den Buuse, M.

BEHAVIORAL PHARMACOLOGY

Estrogen and Progesterone Prevent Disruption of Prepulse Inhibition by the Serotonin-1A Receptor Agonist 8-Hydroxy-2-dipropylaminotetralin

Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Parkville, Australia; and Department of Pharmacology, The University of Melbourne, Melbourne, Australia

The aim of the present study was to investigate the effect of estrogen and progesterone treatment on 5-hydroxytryptamine (serotonin)-1A (5-HT_1A) receptor-mediated disruption of prepulse inhibition (PPI) of acoustic startle. The age-at-onset of schizophrenia is later in women than men, and it has been suggested that women may be protected from schizophrenia by the sex steroid hormone estrogen. 5-HT_1A receptors have been implicated in the development of schizophrenia and the action of antipsychotics. PPI is a model of sensorimotor gating that is deficient in schizophrenia and other illnesses. Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Some OVX rats received silastic implants filled with a low dose of estrogen (E20), a high dose of estrogen (E100), progesterone (P), or both the E20- and P-filled (E/P) silastic implants. Two weeks later, the rats were randomly treated with saline, or 0.02 or 0.5 mg/kg of the 5-HT_1A receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). Treatment with 8-OH-DPAT resulted in a dose-dependent increase in startle amplitude in all rat groups. PPI was significantly reduced after injection of 0.5 mg/kg 8-OH-DPAT in sham-operated rats, untreated OVX rats, E20-treated OVX rats, and P-treated OVX rats. In contrast, in E100- and E/P-treated OVX rats, PPI was not significantly reduced by 0.5 mg/kg 8-OH-DPAT. These data suggest that treatment with a high dose of estrogen, or with a combination of estrogen and progesterone, prevents 8-OH-DPAT-induced disruption of PPI. Thus, these hormones could be protective against sensorimotor gating deficits, at least those induced by 5-HT_1A receptor stimulation, and may therefore be beneficial against some symptoms of schizophrenia.

Address correspondence to: Dr. M. Van den Buuse, Behavioral Neuroscience Laboratory, Mental Health Research Institute of Victoria, 155 Oak St., Parkville, VIC 3052, Australia. E-mail: mvandenbuuse{at}mhri.edu.au

This article has been cited by other articles:

				S. Deurveilher, E. M. Cumyn, T. Peers, B. Rusak, and K. Semba Estradiol replacement enhances sleep deprivation-induced c-Fos immunoreactivity in forebrain arousal regions of ovariectomized rats Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1328 - R1340. [Abstract] [Full Text] [PDF]

				J. S. Brown Jr Effects of Bisphenol-A and Other Endocrine Disruptors Compared With Abnormalities of Schizophrenia: An Endocrine-Disruption Theory of Schizophrenia Schizophr Bull, January 31, 2008; (2008) sbm147v1. [Abstract] [Full Text] [PDF]

				M. van den Buuse and A. Gogos Differential Effects of Antipsychotic Drugs on Serotonin-1A Receptor-Mediated Disruption of Prepulse Inhibition J. Pharmacol. Exp. Ther., March 1, 2007; 320(3): 1224 - 1236. [Abstract] [Full Text] [PDF]