FAAH inhibition produces antidepressant-like efforts of mice to acute stress via synaptic long-term depression
FAAH inhibition produces antidepressant-like efforts of mice to acute stress via synaptic long-term depression
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FAAH 抑制作用使小鼠通过突触长期抑制产生类似抗抑郁药的作用，以应对急性应激
DOI：
10.1016/j.bbr.2017.01.054
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发表时间：
2017-05
影响因子：
2.7
通讯作者：
Zhang Xia
中科院分区：
文献类型：
--
作者：
Wang Ying;Zhang Xia
近年来的研究表明，抑制内源性大麻素N-花生四烯酸乙醇胺（AEA）的主要降解酶脂肪酸酰胺水解酶（FAAH）可产生抗抑郁行为反应，但其机制尚不清楚。在这里，我们发现，FAAH抑制剂PF 3845的全身给药或AEA elevolanin vivolong-term depression（LTD）在海马的兴奋性海马CA 3-CA 1突触的CA 1内应用。通过LTD阻断肽Tat-GluR 2消除PF 3845和/或AEA引起的LTD。PF 3845显著降低了幼稚小鼠对急性不可避免的应激的被动行为应对，这也被Tat-GluR 2肽消除。然而，PF 3845并不显著影响接受皮质酮慢性给药的小鼠的蔗糖假设率。这些结果表明，FAAH抑制剂能够通过LTD在海马CA 3-CA 1突触产生抗抑郁作用，在幼稚动物中响应急性应激。
Recent studies have shown that inhibition of fatty acid amide hydrolase (FAAH), the major degradative enzyme of the endocannabinoidN-arachidonoylethanolamine (AEA), produced antidepressant behavioral responses, but its underlying mechanism is not clear. Here we find that a systemic administration of the FAAH inhibitor PF3845 or an intra-CA1 application of AEA elicits anin vivolong-term depression (LTD) at excitatory glutamatergic CA3-CA1 synapses of the hippocampus. The PF3845- and/or AEA-elicited LTD are abolished by the LTD-blocking peptide Tat-GluR2. PF3845 significantly decreases passive behavioral coping of naïve mice to acute inescapable stress, which is also abolished by Tat-GluR2 peptide. However, PF3845 does not significantly affect sucrose assumption ratio of mice receiving chronic administration of corticosterone. These results suggest that FAAH inhibitors are able to produce antidepressant effects in naïve animals in response to acute stress through LTD at hippocampal glutamatergic CA3-CA1 synapses.
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DOI：
10.1126/science.1241224
发表时间：
2013-10-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Xie L;Kang H;Xu Q;Chen MJ;Liao Y;Thiyagarajan M;O'Donnell J;Christensen DJ;Nicholson C;Iliff JJ;Takano T;Deane R;Nedergaard M
通讯作者：
Nedergaard M
影响因子：
25
作者：
Schlosburg, Joel E.;Blankman, Jacqueline L.;Long, Jonathan Z.;Nomura, Daniel K.;Pan, Bin;Kinsey, Steven G.;Nguyen, Peter T.;Ramesh, Divya;Booker, Lamont;Burston, James J.;Thomas, Elizabeth A.;Selley, Dana E.;Sim-Selley, Laura J.;Liu, Qing-song;Lichtman, Aron H.;Cravatt, Benjamin F.
通讯作者：
Cravatt, Benjamin F.
影响因子：
7.6
作者：
Bambico, Francis Rodriguez;Cassano, Tommaso;Gobbi, Gabriella
通讯作者：
Gobbi, Gabriella
影响因子：
--
作者：
Gourley, Shannon L;Taylor, Jane R
通讯作者：
Taylor, Jane R
影响因子：
56.9
作者：
Huber, KM;Kayser, MS;Bear, MF
通讯作者：
Bear, MF