Nin M S, Salles F B, Azeredo L A, Frazon A P G, Gomez R, Barros H M T
Division of Pharmacology, Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Sarmento Leite, 245, Porto Alegre, RS Brazil.
J Psychopharmacol. 2008 Jul;22(5):477-85. doi: 10.1177/0269881107081525. Epub 2008 Feb 28.
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.
本研究旨在验证双侧海马内注射神经甾体别孕烯醇酮（3α-羟基-5α-孕烷-20-酮；3α, 5α-THP）在强迫游泳试验（FST）以及α4和γ2 GABA(A)受体亚基基因表达方面的作用。结果显示，双侧海马内注射2.5μg/大鼠的别孕烯醇酮（P<0.05）可减少FST中的不动行为并增加攀爬行为。总体而言，对于所测试的所有别孕烯醇酮剂量（1.25、2.5、5.0μg/大鼠），均观察到γ2（P<0.05）GABA(A)亚基mRNA增加。别孕烯醇酮治疗后，右半球γ2基因表达的增加高于左半球（P<0.01）。海马内注射别孕烯醇酮未改变α4亚基的表达。总之，海马内注射别孕烯醇酮在中等剂量时在FST中产生类似抗抑郁的作用，证实了神经甾体作为一类新型抗抑郁药物的潜力。我们的研究结果表明，γ2而非α4 GABA(A)亚基需要进一步评估以参与别孕烯醇酮在海马中的抗抑郁作用，并且该药物的生化作用存在半球差异。
