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Journal of Psychopharmacology
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0269881107081525v1
22/5/477    most recent
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Antidepressant effect and changes of GABAA receptor {gamma}2 subunit mRNA after hippocampal administration of allopregnanolone in rats

MS Nin

Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil

FB Salles

Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil

LA Azeredo

Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil

APG Frazon

Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil

R. Gomez

Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil

HMT Barros

Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil, helenbar{at}fffcmpa.edu.br

The present study aimed to verify the effect of bilateral intra-hippocampus administration of the neurosteroid allopregnanolone (3{alpha}-hydroxy-5{alpha}-pregnan-20-one; 3{alpha}, 5{alpha}-THP) in the forced swimming test (FST) and in the {alpha}4 and {gamma}2 GABAA 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 {gamma}2 (P < 0.05) GABAA subunit mRNA was observed. There was a higher increase in the {gamma}2 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 {alpha}4 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 {gamma}2, but not the {alpha}4 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

This version was published on July 1, 2008

Journal of Psychopharmacology, Vol. 22, No. 5, 477-485 (2008)
DOI: 10.1177/0269881107081525
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