Differential effects of TRPV1 receptor ligands against nicotine-induced depression-like behaviors
Differential effects of TRPV1 receptor ligands against nicotine-induced depression-like behaviors
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DOI：
10.1186/1471-2210-11-6
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发表时间：
2011-07-18
期刊：
影响因子：
--
通讯作者：
Hayase, Tamaki
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文献类型：
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作者：
Hayase, Tamaki
背景：据报道，大脑大麻素 (CB) 受体（通常是 CB1（CB 1 型）受体）对尼古丁 (NC) 行为影响的贡献涉及大脑瞬时受体电位香草酸 1 (TRPV1) 受体，候选内源性 TRPV1 配体的激活预计将具有治疗效果。在本研究中，在小鼠模型中检查了具有或不具有CB1受体亲和力的TRPV1配体对NC诱导的抑郁样行为改变的影响，以阐明TRPV1受体对各种类型的烟草滥用中观察到的NC诱导的“抑郁”的“抗抑郁样”贡献。 结果：重复皮下NC治疗（NC组：0.3 mg/kg，4天），如重复固定应激（IM） （IM 组：10 分钟，4 天），在最后一次治疗后 2 小时的时间点，在强迫游泳（游泳行为减少）和悬尾（增加不动时间）测试中引起抑郁样行为改变。在 NC 组和 IM 组中，腹腔注射 TRPV1 激动剂辣椒素 (CP) 和 olvanil (OL) 对这些行为改变产生了显着的抗抑郁样减弱作用，而 TRPV1 拮抗剂辣椒西平 (CZ) 则没有减弱任何抑郁样行为。此外，内源性 TRPV1 激动剂 CB1 激动剂 anandamide (AEA) 和 N-arachidonyldopamine (NADA) 不具有任何抗抑郁样作用。然而，一种合成的 CB1 和 TRPV1 受体“混合”激动剂 Arvanil (AR) 引起了显着的抗抑郁样作用。 CP 和 OL 的抗抑郁样作用被 TRPV1 拮抗剂 CZ 拮抗。然而，CZ 或 CB1 拮抗剂 AM 251 (AM) 都不能拮抗 AR 的抗抑郁样作用。 结论：本研究中显示的 TRPV1 激动剂的抗抑郁样作用表明 TRPV1 受体在 NC 诱导的抑郁样行为中具有特征性参与，与 IM 引起的行为类似。强效TRPV1加CB1激动剂AR具有强烈的抗抑郁样作用，据报道，AR可能通过非TRPV1或非CB1机制引起部分TRPV1模拟和大麻模拟作用，这支持了其他作用位点的贡献，这可能在NC滥用的治疗中发挥重要的治疗作用。
Background: The contributions of brain cannabinoid (CB) receptors, typically CB1 (CB type 1) receptors, to the behavioral effects of nicotine (NC) have been reported to involve brain transient receptor potential vanilloid 1 (TRPV1) receptors, and the activation of candidate endogenous TRPV1 ligands is expected to be therapeutically effective. In the present study, the effects of TRPV1 ligands with or without affinity for CB1 receptors were examined on NC-induced depression-like behavioral alterations in a mouse model in order to elucidate the "antidepressant-like" contributions of TRPV1 receptors against the NC-induced "depression" observed in various types of tobacco abuse.Results: Repeated subcutaneous NC treatments (NC group: 0.3 mg/kg, 4 days), like repeated immobilization stress (IM) (IM group: 10 min, 4 days), caused depression-like behavioral alterations in both the forced swimming (reduced swimming behaviors) and the tail suspension (increased immobility times) tests, at the 2 h time point after the last treatment. In both NC and IM groups, the TRPV1 agonists capsaicin (CP) and olvanil (OL) administered intraperitoneally provided significant antidepressant-like attenuation against these behavioral alterations, whereas the TRPV1 antagonist capsazepine (CZ) did not attenuate any depression-like behaviors. Furthermore, the endogenous TRPV1-agonistic CB1 agonists anandamide (AEA) and N-arachidonyldopamine (NADA) did not have any antidepressant-like effects. Nevertheless, a synthetic "hybrid" agonist of CB1 and TRPV1 receptors, arvanil (AR), caused significant antidepressant-like effects. The antidepressant-like effects of CP and OL were antagonized by the TRPV1 antagonist CZ. However, the antidepressant-like effects of AR were not antagonized by either CZ or the CB1 antagonist AM 251 (AM).Conclusions: The antidepressant-like effects of TRPV1 agonists shown in the present study suggest a characteristic involvement of TRPV1 receptors in NC-induced depression-like behaviors, similar to those caused by IM. The strong antidepressant-like effects of the potent TRPV1 plus CB1 agonist AR, which has been reported to cause part of its TRPV1-mimetic and cannabimimetic effects presumably via non-TRPV1 or non-CB1 mechanisms support a contribution from other sites of action which may play a therapeutically important role in the treatment of NC abuse.