Antidepressant effect and changes of GABAA receptor γ2 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 GABAA receptor subunits gene expression. Results showed that bilateral int...

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Bibliographic Details
Published in:Journal of psychopharmacology (Oxford) 2008-07, Vol.22 (5), p.477-485
Main Authors: Nin, MS, Salles, FB, Azeredo, LA, Frazon, APG, Gomez, R., Barros, HMT
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Biological and medical sciences
Depression
Medical sciences
Mood disorders
Neuropharmacology
Pharmacology. Drug treatments
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychopharmacology
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Summary: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 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 γ2 (P < 0.05) GABAA 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 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.
ISSN:0269-8811
1461-7285
DOI:10.1177/0269881107081525