Effect of progesterone on the expression of GABA(A)  receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere.
Progesterone is a neuroactive hormone with non-genomic effects on GABA(A) receptors (GABA(A)R). Changes in the expression of GABA(A)R 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 GABA(A)R 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 GABA(A)R α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABA(A)R γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABA(A) system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABA(A) R α1 subunit expression in the right prefrontal cortex of female rats.
Department of Physiology, Universidade Federal do Rio Grande do Sul-UFRGS, Porto Alegre, Rio Grande do Sul Brazil.
Susie
S
Andrade
Bruno D
BD
Arbo
Bruna A M
BA
Batista
Alice M
AM
Neves
Gisele
G
Branchini
Ilma S
IS
Brum
Helena M T
HM
Barros
Rosane
R
Gomez
Maria Flavia M
MF
Ribeiro
D000704:Analysis of Variance; D000818:Animals; D004031:Diestrus / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013550:Swimming; D013997:Time Factors
D011372:Progestins; D021122:Protein Subunits; D011963:Receptors, GABA-A; D011374:Progesterone