Transient receptor potential vanilloid 1 channels modulate the anxiolytic effect of diazepam
Transient receptor potential vanilloid 1 channels modulate the anxiolytic effect of diazepam
复制标题
DOI：
10.1016/j.brainres.2011.09.049
复制
发表时间：
2011-11-24
期刊：
影响因子：
2.9
通讯作者：
Umathe, Sudhir N.
中科院分区：
文献类型：
--
作者：
Manna, Shyamshree S. S.;Umathe, Sudhir N.
本研究探讨了香草酸和GABA能系统在焦虑中的相互作用。在脑室内单独或与传统抗焦虑药物地西泮组合施用辣椒素（TRPV 1激动剂）或辣椒平（TRPV 1拮抗剂）后，对瑞士小鼠进行社交互动测试，这是用于评估焦虑相关行为的动物模型。结果表明，辣椒素（1，10和100 μ g/小鼠）减少了相互作用时间，表现出焦虑样反应，而辣椒平（10和100 μ g/小鼠）产生类似于地西泮（0.25-4 mg/kg，i.p）的抗焦虑样反应。在此之前给予辣椒素本身无活性的剂量（0.1 μ g/小鼠）减弱了地西泮的抗焦虑作用，而辣椒平和地西泮以其亚有效剂量以及有效剂量共同给药表现出显著的抗焦虑样作用。有趣的是，地西泮（2 mg/kg）和辣椒平（100 μ g/小鼠）的联合治疗没有产生镇静或运动缺陷效应。相反，发现单独较高剂量的地西泮（>2 mg/kg）具有镇静或运动抑制作用，表明地西泮的抗焦虑作用至少部分涉及TRPV 1受体。此外，辣椒平预处理阻断了辣椒素（1和100 μ g/小鼠）的致焦虑作用。总之，这些发现表明，阻断TRPV 1可能是预防与长期使用苯二氮卓类药物相关风险的功能性工具。(C)2011 Elsevier B. V.保留所有权利。
The present study investigated the interaction between the vanilloid and GABAergic systems on anxiety. Swiss mice were subjected to social interaction test, an animal model for assessing anxiety-related behavior, after intracerebroventicular administration of capsaicin, (TRPV1 agonist) or capsazepine, (TRPV1 antagonist) either alone or in combination with traditional anxiolytic drug, diazepam. Results showed that capsaicin (1, 10, and 100 mu g/mouse) decreased the interaction time exhibiting an anxiogenic-like response, while capsazepine (10, and 100 mu g/mouse) produced anxiolytic-like response similar to that of diazepam (0.25-4 mg/kg, i.p). Prior administration of capsaicin at a dose, inactive per se (0.1 mu g/mouse) attenuated the anxiolytic effect of diazepam, whereas, co-administration of capsazepine and diazepam both in their sub-effective as well as effective doses exhibited significant anxiolytic-like effect. Interestingly, the combined treatment of diazepam (2 mg/kg) and capsazepine (100 mu g/mouse) produced no sedative or locomotor deficit effects. On the contrary, a higher dose of diazepam (>2 mg/kg) alone was found to be a sedative or locomotor depressant, indicating that the anxiolytic effect of diazepam, at least in part involve TRPV1 receptor. Morever, capsazepine pretreatment blocked the anxiogenic effect of capsaicin (1, and 100 mu g/mouse). Taken together, these findings suggest that blockade of TRPV1 might be a functional tool to prevent the risks associated with the long-term use of benzodiazepines. (C) 2011 Elsevier B.V. All rights reserved.