The effect of intra-nucleus accumbens administration of allopregnanolone on δ and γ2 GABA(A) receptor subunit mRNA expression in the hippocampus and on depressive-like and grooming behaviors in rats.

ABSTRACT

Alterations in GABA(A) receptor expression have been associated with the allopregnanolone (3α-hydroxy-5α-pregnan-20-one; 3α,5α-THP) antidepressant-like effect in rats. The present study aimed to verify the effect of bilateral, intra-nucleus accumbens core (intra-AcbC) administration of the neurosteroid allopregnanolone on behaviors in the forced swim and grooming microstructure tests and in the δ and γ2 GABA(A) receptor subunit mRNA expression in right and left hippocampus of rats. The results of this study showed that bilateral, intra-AcbC allopregnanolone administration (5µg/rat) presented antidepressant-like activity in the forced swim test concomitant with an increase in climbing. Allopregnanolone at doses of 1.25 and 5µg/rat also decreased the percentage of correct transitions in the grooming microstructure test. Both δ and γ2 GABA(A) subunit expressions increased in the rat hippocampus after allopregnanolone intra-AcbC treatment. Our findings point to asymmetrical GABA(A) receptor expression changes in the hippocampus of animals treated with allopregnanolone. Further investigation should evaluate the antidepressant-like effect of allopregnanolone not only in other directly infused regions but also with respect to changes in other brain areas of the limbic system to understand allopregnanolone's mechanism of action.