Antidepressant effect and changes of GABAA receptor gamma2 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 (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.
Nin
M S
MS
Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil.
Salles
F B
FB
Azeredo
L A
LA
Frazon
A P G
AP
Gomez
R
R
Barros
H M T
HM
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D011280:Pregnanolone / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013550:Swimming
D000928:Antidepressive Agents; C546262:Gabra4 protein, rat; C546281:Gabrg2 protein, rat; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011280:Pregnanolone