Effect of progesterone on the expression of GABAA receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere

• Published in: Cell biochemistry and function 2012-12, Vol.30 (8), p.696-700
• Main Authors: Andrade, Susie, Arbo, Bruno D., Batista, Bruna A. M., Neves, Alice M., Branchini, Gisele, Brum, Ilma S., Barros, Helena M. T., Gomez, Rosane, Ribeiro, Maria Flavia M.
• Format: Article
• Language: English
• Subjects: asymmetry; depression; GABA agonist; mood disorders; neuroactive steroids
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.2854

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.