Antidepressant effect and changes of GABA A receptor γ2 subunit mRNA after hippocampal administration of allopregnanolone in rats

Abstract

The present study aimed to verify the effect of bilateral intra-hippocampus administration of the neurosteroid allopregnanolone (3α-hydroxy-5α-pregnan-20-one; 3α, 5α-THP) in the forced swimming test (FST) and in the α4 and γ2 GABA_A receptor subunits gene expression. Results showed that bilateral intra-hippocampal allopregnanolone administration of 2.5 μg/rat ( P < 0.05) reduced immobile behavior and increased climbing behavior in the FST. Overall, for all doses of allopregnanolone tested (1.25, 2.5, 5.0 μg/rat), an increase of γ2 (P < 0.05) GABA_A subunit mRNA was observed. There was a higher increase in the γ2 gene expression in the right hemisphere than in the left hemisphere (P < 0.01) after allopregnanolone treatment. Intra-hippocampal allopregnanolone did not change the expression of the α4 subunits. In conclusion, intra-hippocampal administration of allopregnanolone produces an antidepressant-like effect in the FST at an intermediate dose, confirming the potential of neurosteroids as a new class of antidepressant drugs. Our findings suggest that the γ2, but not the α4 GABA_A subunit, needs further evaluation to be involved in the antidepressant effect of allopregnanolone in the hippocampus and that there is a hemispheric diversity in the biochemical effect of the drug.