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Antidepressant effect and changes of GABAA receptor gamma2 subunit mRNA after hippocampal administration of allopregnanolone in rats.
J Psychopharmacol. 2008 Jul; 22(5):477-85.JP

Abstract

The present study aimed to verify the effect of bilateral intra-hippocampus administration of the neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one; 3alpha, 5alpha-THP) in the forced swimming test (FST) and in the alpha4 and gamma2 GABA(A) receptor subunits gene expression. Results showed that bilateral intra-hippocampal allopregnanolone administration of 2.5 microg/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 microg/rat), an increase of gamma2 (P<0.05) GABA(A) subunit mRNA was observed. There was a higher increase in the gamma2 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 alpha4 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 gamma2, but not the alpha4 GABA(A) 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.

Authors+Show Affiliations

Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18308780

Citation

Nin, M S., et al. "Antidepressant Effect and Changes of GABAA Receptor Gamma2 Subunit mRNA After Hippocampal Administration of Allopregnanolone in Rats." Journal of Psychopharmacology (Oxford, England), vol. 22, no. 5, 2008, pp. 477-85.
Nin MS, Salles FB, Azeredo LA, et al. Antidepressant effect and changes of GABAA receptor gamma2 subunit mRNA after hippocampal administration of allopregnanolone in rats. J Psychopharmacol (Oxford). 2008;22(5):477-85.
Nin, M. S., Salles, F. B., Azeredo, L. A., Frazon, A. P., Gomez, R., & Barros, H. M. (2008). Antidepressant effect and changes of GABAA receptor gamma2 subunit mRNA after hippocampal administration of allopregnanolone in rats. Journal of Psychopharmacology (Oxford, England), 22(5), 477-85. https://doi.org/10.1177/0269881107081525
Nin MS, et al. Antidepressant Effect and Changes of GABAA Receptor Gamma2 Subunit mRNA After Hippocampal Administration of Allopregnanolone in Rats. J Psychopharmacol (Oxford). 2008;22(5):477-85. PubMed PMID: 18308780.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant effect and changes of GABAA receptor gamma2 subunit mRNA after hippocampal administration of allopregnanolone in rats. AU - Nin,M S, AU - Salles,F B, AU - Azeredo,L A, AU - Frazon,A P G, AU - Gomez,R, AU - Barros,H M T, Y1 - 2008/02/28/ PY - 2008/3/1/pubmed PY - 2008/12/17/medline PY - 2008/3/1/entrez SP - 477 EP - 85 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 22 IS - 5 N2 - The present study aimed to verify the effect of bilateral intra-hippocampus administration of the neurosteroid allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one; 3alpha, 5alpha-THP) in the forced swimming test (FST) and in the alpha4 and gamma2 GABA(A) receptor subunits gene expression. Results showed that bilateral intra-hippocampal allopregnanolone administration of 2.5 microg/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 microg/rat), an increase of gamma2 (P<0.05) GABA(A) subunit mRNA was observed. There was a higher increase in the gamma2 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 alpha4 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 gamma2, but not the alpha4 GABA(A) 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. SN - 0269-8811 UR - https://www.unboundmedicine.com/medline/citation/18308780/Antidepressant_effect_and_changes_of_GABAA_receptor_gamma2_subunit_mRNA_after_hippocampal_administration_of_allopregnanolone_in_rats_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881107081525?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -