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Antidepressant effect and changes of GABA_A receptor 2 subunit mRNA after hippocampal administration of allopregnanolone in rats

Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, PC 90050–170 Porto Alegre, RS Brazil.

^* To whom correspondence should be addressed.

	Abstract

The present study aimed to verify the effect of bilateral intrahippocampus administration of the neurosteroid allopregnanolone (3a–hydroxy–5a–pregnan–20–one; 3a, 5a–THP) in the forced swimming test (FST) and in the a4 and g2 GABAA receptor subunits gene expression. Results showed that bilateral intra–hippocampal allopregnanolone administration of 2.5mg/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, 5.0mg/rat), an increase of g2 (P , 0.05) GABAA subunit mRNA was observed. There was a higher increase in the g2 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 a4 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 g2, but not the a4 GABAA 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.

Key Words: allopregnanolone, forced swim test, GABAA receptor, depression, gamma2, alpha4

First published on February 28, 2008, doi:10.1177/0269881107081525

Journal of Psychopharmacology 2008;22:477.

A more recent version of this article appeared on July 1, 2008


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