Antidepressant effect and changes of GABA^sub A^ receptor [gamma]2 subunit mRNA after hippocampal administration of allopregnanolone in rats

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 GABAsubA 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) GABAsubA 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 GABAsubA 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. [PUBLICATION ABSTRACT]