Anxiolytic-like effects induced by blockade of transient receptor potential vanilloid type 1 (TRPV1) channels in the medial prefrontal cortex of rats
Anxiolytic-like effects induced by blockade of transient receptor potential vanilloid type 1 (TRPV1) channels in the medial prefrontal cortex of rats
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DOI：
10.1007/s00213-009-1532-5
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发表时间：
2009-08-01
影响因子：
3.4
通讯作者：
Moreira, Fabricio A.
中科院分区：
文献类型：
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作者：
Aguiar, Daniele C.;Terzian, Ana Luisa B.;Moreira, Fabricio A.
内源性大麻素anandamide，除了激活大麻素1型受体（CB 1），可以作为一种激动剂在瞬时受体电位香草素1型（TRPV 1）通道。在中脑导水管周围灰质，CB 1激活抑制，而TRPV 1增加，焦虑样行为。在内侧前额叶皮层（mPFC），另一个与防御反应相关的大脑区域，CB 1激活诱导抗焦虑作用。然而，TRPV 1的可能参与仍然不清楚。在本研究中，我们检验了TRPV 1通道有助于调节mPFC中焦虑样行为的假设。雄性Wistar大鼠（每组n = 5-7）接受TRPV 1拮抗剂辣椒平的微量注射（1-60 nmol）的mPFC腹侧部分，并暴露于高架十字迷宫（高架十字迷宫）Capsazepine增加了大鼠对张开双臂的探索，以及Vogel冲突测试中惩罚性舔的数量，表明具有抗焦虑作用。在闭合臂中没有观察到进入次数的变化，表明运动活动没有变化。此外，辣椒平不会干扰饮水量或伤害性阈值，从而排除了Vogel冲突测试的潜在混杂因素。这些数据表明腹侧mPFC中的TRPV 1可以强直性抑制焦虑样行为。TRPV 1可以促进防御反应，从而对抗CB 1受体局部激活后报告的抗焦虑样作用。
The endocannabinoid anandamide, in addition to activating cannabinoid type 1 receptors (CB1), may act as an agonist at transient receptor potential vanilloid type 1 (TRPV1) channels. In the periaqueductal gray, CB1 activation inhibits, whereas TRPV1 increases, anxiety-like behavior. In the medial prefrontal cortex (mPFC), another brain region related to defensive responses, CB1 activation induces anxiolytic-like effects. However, a possible involvement of TRPV1 is still unclear.In the present study, we tested the hypothesis that TRPV1 channel contributes to the modulation of anxiety-like behavior in the mPFC.Male Wistar rats (n = 5-7 per group) received microinjections of the TRPV1 antagonist capsazepine (1-60 nmol) in the ventral portion of the mPFC and were exposed to the elevated plus maze (EPM) or to the Vogel conflict test.Capsazepine increased exploration of open arms in the EPM as well as the number of punished licks in the Vogel conflict test, suggesting anxiolytic-like effects. No changes in the number of entries into the enclosed arms were observed in the EPM, indicating that there were no changes in motor activity. Moreover, capsazepine did not interfere with water consumption or nociceptive threshold, discarding potential confounding factors for the Vogel conflict test.These data suggest that TRPV1 in the ventral mPFC tonically inhibits anxiety-like behavior. TRPV1 could facilitate defensive responses opposing, therefore, the anxiolytic-like effects reported after local activation of CB1 receptors.