Programa de Pós Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Sarmento Leite, 245, 90050-170, Porto Alegre, RS, Brazil.
Pharmacol Biochem Behav. 2012 Dec;103(2):359-66. doi: 10.1016/j.pbb.2012.09.002. Epub 2012 Sep 7.
Alterations in GABA(A) receptor expression have been associated with the allopregnanolone (3α-hydroxy-5α-pregnan-20-one; 3α,5α-THP) antidepressant-like effect in rats. The present study aimed to verify the effect of bilateral, intra-nucleus accumbens core (intra-AcbC) administration of the neurosteroid allopregnanolone on behaviors in the forced swim and grooming microstructure tests and in the δ and γ2 GABA(A) receptor subunit mRNA expression in right and left hippocampus of rats. The results of this study showed that bilateral, intra-AcbC allopregnanolone administration (5μg/rat) presented antidepressant-like activity in the forced swim test concomitant with an increase in climbing. Allopregnanolone at doses of 1.25 and 5μg/rat also decreased the percentage of correct transitions in the grooming microstructure test. Both δ and γ2 GABA(A) subunit expressions increased in the rat hippocampus after allopregnanolone intra-AcbC treatment. Our findings point to asymmetrical GABA(A) receptor expression changes in the hippocampus of animals treated with allopregnanolone. Further investigation should evaluate the antidepressant-like effect of allopregnanolone not only in other directly infused regions but also with respect to changes in other brain areas of the limbic system to understand allopregnanolone's mechanism of action.
GABA(A) 受体表达的改变与异孕烯醇酮(3α-羟基-5α-孕烷-20-酮;3α,5α-THP)在大鼠中的抗抑郁作用有关。本研究旨在验证神经甾体异孕烯醇酮双侧核内伏隔核核心(双侧 intra-AcbC)给药对大鼠强迫游泳和梳理微观结构测试中的行为以及右左海马中 δ 和 γ2 GABA(A) 受体亚基 mRNA 表达的影响。本研究结果表明,双侧 intra-AcbC 异孕烯醇酮给药(5μg/大鼠)在强迫游泳试验中表现出抗抑郁样活性,同时增加了攀爬。异孕烯醇酮剂量为 1.25 和 5μg/大鼠也降低了梳理微观结构测试中正确转变的百分比。异孕烯醇酮 intra-AcbC 处理后,大鼠海马中 δ 和 γ2 GABA(A) 亚基表达增加。我们的发现表明,异孕烯醇酮处理后的动物海马中 GABA(A) 受体表达存在不对称变化。进一步的研究应该评估异孕烯醇酮的抗抑郁样作用,不仅在其他直接输注的区域,而且在边缘系统的其他脑区的变化方面,以了解异孕烯醇酮的作用机制。