Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 3900 Bandeirantes av., Monte Alegre, Ribeirão Preto, São Paulo, Brazil.
Psychopharmacology (Berl). 2013 Mar;226(1):13-24. doi: 10.1007/s00213-012-2878-7. Epub 2012 Sep 25.
Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood.
The present study evaluates the role of the serotonergic neurotransmission within the DPAG in the modulation of escape responses of rats chronically treated with CBD.
Male Wistar rats received acute or repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the elevated T-maze (ETM). We also investigated if CBD effects on the ETM depend on facilitation of 5-HT1A-mediated neurotransmission in the DPAG. To this latter aim, we verified if these effects would be prevented by intra-DPAG injection of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol/0.2 μL). Also, we verified, by in vivo microdialysis, if CBD chronic treatment increases serotonin (5-HT) release and, by quantitative polymerase chain reaction, if there are changes in 5HT-1A or 5HT-2C mRNA expression in DPAG.
The results showed that repeated but not acute peripheral administration of CBD decreases escape responses in the ETM, suggesting a panicolytic effect. This treatment did not change 5HT-1A or 5-HT-2C receptor mRNA expression nor modify serotonin extracellular concentrations in the DPAG. CBD effects were prevented by DPAG injection of the 5-HT1A receptor antagonist.
Together, these findings suggest that repeated treatment with CBD induces anti-panic effects by acting on 5-HT1A receptors in DPAG.
大麻二酚（CBD）是大麻植物的非致幻成分，在急性全身或背侧导水管周围灰质（DPAG）内给药后，可在动物模型中促进抗焦虑和抗惊恐作用。然而，在焦虑和惊恐相关反应的动物模型中，CBD 的重复给药及其可能涉及的机制仍知之甚少。
本研究评估 DPAG 内 5-羟色胺能神经传递在慢性 CBD 治疗大鼠逃避反应调节中的作用。
雄性 Wistar 大鼠接受 CBD 的急性或重复（5mg/kg/天/21 天）给药，并进行高架 T 迷宫（ETM）测试。我们还研究了 CBD 对 ETM 的影响是否取决于 DPAG 中 5-HT1A 介导的神经传递的促进。为此，我们验证了 DPAG 内注射 5-HT1A 受体拮抗剂 WAY100635（0.37nmol/0.2μL）是否会阻止这些影响。此外，我们通过体内微透析验证了 CBD 慢性治疗是否会增加 DPAG 中的 5-羟色胺（5-HT）释放，以及通过定量聚合酶链反应是否会改变 DPAG 中的 5-HT1A 或 5-HT2C mRNA 表达。
结果表明，重复而非急性外周 CBD 给药可减少 ETM 中的逃避反应，提示具有抗惊恐作用。这种治疗不会改变 5-HT1A 或 5-HT2C 受体 mRNA 表达，也不会改变 DPAG 中 5-HT 的细胞外浓度。DPAG 内注射 5-HT1A 受体拮抗剂可阻止 CBD 作用。
综上所述，这些发现表明，CBD 的重复治疗通过作用于 DPAG 中的 5-HT1A 受体，诱导抗惊恐作用。
