Effect of genetic and pharmacological blockade of GABA receptors on the 5-HT2C receptor function during stress.
Effect of genetic and pharmacological blockade of GABA receptors on the 5-HT2C receptor function during stress.
复制标题
DOI：
10.1111/jnc.12929
复制
发表时间：
2014-12
影响因子：
4.7
通讯作者：
Mongeau R
中科院分区：
文献类型：
--
作者：
Martin CB;Gassmann M;Chevarin C;Hamon M;Rudolph U;Bettler B;Lanfumey L;Mongeau R
5-HT 2C受体在精神情感障碍中发挥作用，并且通常有助于精神药物的抗抑郁和抗焦虑作用。在应激过程中，这些受体的激活对5-羟色胺（5-HT）的释放产生负反馈，可能是通过增加GABA能中间神经元的活性。然而，迄今为止，介导5-HT 2C受体诱导的反馈抑制的GABA受体类型仍然未知。为了解决这个问题，我们评估了5-HT 2C受体激动剂（RO 60-0175）在海马水平和应激条件下，在小鼠中GABA-A或GABA-B受体的药理学或遗传失活后对5-HT周转的抑制作用。GABA-B受体拮抗剂phaclofen和GABA-B1 a或GABA-B1 b亚基的特异性基因消融均未改变RO 60-0175的抑制作用，尽管在基础和应激条件下GABA-B1 a敲除小鼠中5-HT周转率显著降低。与此相反，5-HT 2C受体介导的抑制5-HT周转减少GABA-A受体拮抗剂荷包牡丹碱。由于5-HT 2C受体激活的显著效应在GABA-A受体α3亚基缺陷的突变小鼠中持续存在，因此可以推断，不含α3亚基的GABA-A受体，而不是GABA-B受体，介导了5-HT 2C诱导的对应激诱导的小鼠海马5-HT更新增加的抑制。
5-HT2C receptors play a role in psychoaffective disorders and often contribute to the antidepressant and anxiolytic effects of psychotropic drugs. During stress, activation of these receptors exerts a negative feedback on serotonin (5-HT) release, probably by increasing the activity of GABAergic interneurons. However, to date, the GABA receptor types that mediate the 5-HT2C receptor-induced feedback inhibition are still unknown. To address this question, we assessed the inhibition of 5-HT turnover by a 5-HT2C receptor agonist (RO 60-0175) at the hippocampal level and under conditions of stress, after pharmacological or genetic inactivation of either GABA-A or GABA-B receptors in mice. Neither the GABA-B receptor antagonist phaclofen nor the specific genetic ablation of either GABA-B1a or GABA-B1b subunits altered the inhibitory effect of RO 60-0175, although 5-HT turnover was markedly decreased in GABA-B1a knock-out mice in both basal and stress conditions. In contrast, the 5-HT2C receptor-mediated inhibition of 5-HT turnover was reduced by the GABA-A receptor antagonist bicuculline. Because a significant effect of 5-HT2C receptor activation persisted in mutant mice deficient in the α3 subunit of GABA-A receptors, it can be inferred that non α3 subunit-containing GABA-A receptors, but not GABA-B receptors, mediate the 5-HT2C-induced inhibition of stress-induced increase of hippocampal 5-HT turnover in mice.
登录
查看更多内容
影响因子：
3.7
作者：
Bubar MJ;Stutz SJ;Cunningham KA
通讯作者：
Cunningham KA
DOI：
10.1073/pnas.89.15.6726
发表时间：
1992-08-01
影响因子：
11.1
作者：
FRITSCHY, JM;BENKE, D;MOHLER, H
通讯作者：
MOHLER, H
影响因子：
3.4
作者：
Dalvi, A;Rodgers, RJ
通讯作者：
Rodgers, RJ
影响因子：
4.7
作者：
Mongeau, Raymond;Martin, Cedric B. P.;Lanfumey, Laurence
通讯作者：
Lanfumey, Laurence
影响因子：
7.3
作者：
Queree, P.;Peters, S.;Sharp, T.
通讯作者：
Sharp, T.