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Effect of progesterone on the expression of GABAA receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere
Authors:Susie Andrade  Bruno D Arbo  Bruna A M Batista  Alice M Neves  Gisele Branchini  Ilma S Brum  Helena M T Barros  Rosane Gomez  Maria Flavia M Ribeiro
Institution:1. Graduate Program in Biological Sciences: Physiology, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), , Porto Alegre, Rio Grande do Sul, Brazil;2. Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), , Porto Alegre, Rio Grande do Sul, Brazil;3. Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), , Porto Alegre, Rio Grande do Sul, Brazil;4. Department of Pharmacology, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), , Porto Alegre, Rio Grande do Sul, Brazil
Abstract:Progesterone is a neuroactive hormone with non‐genomic effects on GABAA receptors (GABAAR). Changes in the expression of GABAAR subunits are related to depressive‐like behaviors in rats. Moreover, sex differences and depressive behaviors have been associated with prefrontal brain asymmetry in rodents and humans. Thus, our objective was to investigate the effect of progesterone on the GABAAR α1 and γ2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female and male rats exposed to the forced swimming test (FST). Male and female rats (n = 8/group) were randomly selected to receive a daily dose of progesterone (0·4 mg·kg–1) or vehicle, during two complete female estrous cycles (8–10 days). On the experiment day, male rats or diestrus female rats were euthanized 30 min after the FST. Our results showed that progesterone significantly increased the α1 subunit mRNA in both hemispheres of male and female rats. Moreover, there was an inverse correlation between depressive‐like behaviors and GABAAR α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABAAR γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABAA system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABAAR α1 subunit expression in the right prefrontal cortex of female rats. Copyright © 2012 John Wiley & Sons, Ltd.
Keywords:GABA agonist  neuroactive steroids  asymmetry  depression  mood disorders
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