Depressive behavior in the forced swim test can be induced by TRPV1 receptor activity and is dependent on NMDA receptors.
Depressive behavior in the forced swim test can be induced by TRPV1 receptor activity and is dependent on NMDA receptors.
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DOI：
10.1016/j.phrs.2013.10.006
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发表时间：
2014-01
影响因子：
9.3
通讯作者：
Larson, Alice A.
中科院分区：
文献类型：
--
作者：
Abdelhamid, Ramy E.;Kovacs, Katalin J.;Nunez, Myra G.;Larson, Alice A.
阻断、脱敏或敲除瞬时受体电位香草酸1型（TRPV 1）受体可降低强迫游泳试验（抑郁行为的一种测量方法）中的不动性。我们质疑增强TRPV 1活性是否能以抗抑郁药所阻止的方式促进不动。为了测试这一点，我们通过比体温（41°C）温暖的水或低剂量的树脂毒素（RTX）激活了小鼠中的热敏TRPV 1受体。41°C的水比较冷的水（26°C）引起较少的不动性，表明体温调节位点对不动性没有贡献。尽管RTX的脱敏方案（3-5次注射0.1mg/kg s.c.）在26°C下游泳时不动性降低，而在41°C下游泳时则没有。相比之下，低剂量RTX（0.02 mg/kg皮下注射）增强不动性，但仅在41°C游泳期间。因此，内源性或外源性TRPV 1受体的激活增强了不动性，并且这些位点被寒冷而不是温暖激活。两种不同类型的抗抑郁药，阿米替林（10 mg/kg i. p.）和氯胺酮（50 mg/kg i. p.），每一种都抑制了低剂量RTX诱导的不动性增加，验证了TRPV 1位点的介导作用。当使用鞘内注射RTX（0.25 μg/kg i.t.）对中心人群进行脱敏时，不动性在两种温度下都减弱，并且由低剂量RTX产生的不动性的增加被抑制。这证明了中枢TRPV 1受体在抑郁行为中的作用，其被条件（冷应激）激活，与沿着热感觉传入（热）激活TRPV 1受体的条件不同。
Blocking, desensitizing, or knocking out transient receptor potential vanilloid type 1 (TRPV1) receptors decreases immobility in the forced swim test, a measure of depressive behavior. We questioned whether enhancing TRPV1 activity promotes immobility in a fashion that is prevented by antidepressants. To test this we activated heat-sensitive TRPV1 receptors in mice by water that is warmer than body temperature (41°C) or a low dose of resiniferatoxin (RTX). Water at 41°C elicited less immobility than cooler water (26°C), indicating that thermoregulatory sites do not contribute to immobility. Although a desensitizing regimen of RTX (3–5 injections of 0.1 mg/kg s.c.) decreased immobility during swims at 26°C, it did not during swims at 41°C. In contrast, low dose of RTX (0.02 mg/kg s.c.) enhanced immobility, but only during swims at 41°C. Thus, activation of TRPV1 receptors, endogenously or exogenously, enhances immobility and these sites are activated by cold rather than warmth. Two distinct types of antidepressants, amitriptyline (10 mg/kg i.p.) and ketamine (50 mg/kg i.p.), each inhibited the increase in immobility induced by the low dose of RTX, verifying its mediation by TRPV1 sites. When desensitization was limited to central populations using intrathecal injections of RTX (0.25 µg/kg i.t.), immobility was attenuated at both temperatures and the increase in immobility produced by the low dose of RTX was inhibited. This demonstrates a role for central TRPV1 receptors in depressive behavior, activated by conditions (cold stress) distinct from those that activate TRPV1 receptors along thermosensory afferents (heat).
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
4.7
作者：
Abdelhamid RE;Kovacs KJ;Pasley JD;Nunez MG;Larson AA
通讯作者：
Larson AA
DOI：
10.1186/1472-6874-5-2
发表时间：
2005-03-08
期刊：
BMC women's health
影响因子：
--
作者：
Gopinath, Preethi;Wan, Elaine;Anand, Praveen
通讯作者：
Anand, Praveen
影响因子：
9.3
作者：
Arai, I;Tsuyuki, Y;Otomo, S
通讯作者：
Otomo, S
影响因子：
3.4
作者：
Bechtholt-Gompf, Anita J.;Smith, Karen L.;Oenguer, Dost
通讯作者：
Oenguer, Dost