Aguiar Daniele C, Terzian Ana Luisa B, Guimarães Francisco S, Moreira Fabrício A
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP 14049-900, Brazil.
Psychopharmacology (Berl). 2009 Aug;205(2):217-25. doi: 10.1007/s00213-009-1532-5. Epub 2009 Apr 22.
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.
内源性大麻素花生四烯乙醇胺,除了激活1型大麻素受体(CB1)外,还可能作为瞬时受体电位香草酸受体1型(TRPV1)通道的激动剂。在导水管周围灰质中,CB1激活会抑制焦虑样行为,而TRPV1激活则会增加焦虑样行为。在内侧前额叶皮质(mPFC),另一个与防御反应相关的脑区,CB1激活会诱导抗焦虑样效应。然而,TRPV1是否参与其中仍不清楚。
在本研究中,我们测试了TRPV1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只)在mPFC腹侧接受TRPV1拮抗剂辣椒素(1 - 60 nmol)的微量注射,并接受高架十字迷宫(EPM)或Vogel冲突试验。
辣椒素增加了大鼠在EPM中对开放臂的探索以及在Vogel冲突试验中受罚舔舐的次数,表明具有抗焦虑样效应。在EPM中,未观察到进入封闭臂的次数有变化,表明运动活动没有改变。此外,辣椒素不影响水消耗或伤害性感受阈值,排除了Vogel冲突试验中潜在的混杂因素。
这些数据表明,腹侧mPFC中的TRPV1持续抑制焦虑样行为。因此,TRPV1可能促进防御反应,与局部激活CB1受体后报道的抗焦虑样效应相反。