Moreira F A, Aguiar D C, Campos A C, Lisboa S F, Terzian A L, Resstel L B, Guimarães F S
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes 3900, 14049900 Ribeirão Preto, SP, Brazil.
Neural Plast. 2009;2009:625469. doi: 10.1155/2009/625469. Epub 2008 Dec 2.
Cannabinoids play an important role in activity-dependent changes in synaptic activity and can interfere in several brain functions, including responses to aversive stimuli. The regions responsible for their effects, however, are still unclear. Cannabinoid type 1 (CB1) receptors are widely distributed in the central nervous system and are present in the periaqueductal gray (PAG), a midbrain structure closely involved in responses related to aversive states. Accordingly, exposure to stressful stimuli increases endocannabinoid (eCB) levels in the PAG, and local administration of CB1 agonists or drugs that facilitate eCB-mediated neurotransmission produces antinociceptive and antiaversive effects. To investigate if these drugs would also interfere in animal models that are sensitive to anxiolytic drugs, we verified the responses to intra-PAG injection of CB1 agonists in rats submitted to the elevated plus-maze, the Vogel punished licking test, or contextual aversive conditioning model. The drugs induced anxiolytic-like effects in all tests. The same was observed with the transient receptor potential vanilloid type 1 (TRPV1) antagonist capsazepine and with cannabidiol, a nonpsychotomimetic phytocannabinoid that produces anxiolytic-like effects after systemic administration in humans and laboratory animals. These results, therefore, suggest that the PAG could be an important site for the antiaversive effects of cannabinoids.
大麻素在依赖活动的突触活动变化中起重要作用，并可干扰多种脑功能，包括对厌恶刺激的反应。然而，其发挥作用的区域仍不清楚。1型大麻素（CB1）受体广泛分布于中枢神经系统，在中脑导水管周围灰质（PAG）中也有表达，PAG是一个与厌恶状态相关反应密切相关的中脑结构。因此，暴露于应激刺激会增加PAG中的内源性大麻素（eCB）水平，局部给予CB1激动剂或促进eCB介导的神经传递的药物会产生抗伤害感受和抗厌恶作用。为了研究这些药物是否也会干扰对抗焦虑药物敏感的动物模型，我们在接受高架十字迷宫、Vogel厌恶舔舐试验或情境厌恶条件反射模型的大鼠中，验证了向PAG内注射CB1激动剂后的反应。这些药物在所有试验中均诱导出抗焦虑样效应。瞬时受体电位香草酸亚型1（TRPV1）拮抗剂辣椒素和大麻二酚（一种在人和实验动物全身给药后产生抗焦虑样效应的非精神致幻植物大麻素）也观察到了同样的结果。因此，这些结果表明，PAG可能是大麻素产生抗厌恶作用的重要部位。
