Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats
Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats
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DOI：
10.1007/s00213-012-2878-7
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发表时间：
2013-03-01
影响因子：
3.4
通讯作者：
Guimaraes, Francisco Silveira
中科院分区：
文献类型：
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作者：
Campos, Alline Cristina;Soares, Vanessa de Paula;Guimaraes, Francisco Silveira
大麻二酚（CBD）是大麻植物的非拟精神病成分，其在急性全身或背侧导水管周围灰质（DPAG）施用后在动物模型中促进抗焦虑和抗恐慌作用。然而，CBD重复给药的影响及其可能的机制，本研究评价了DPAG内的多巴胺能神经传递在慢性CBD处理大鼠逃避反应的调节中的作用。雄性Wistar大鼠接受急性或重复的CBD处理，（5 mg/Kg/每日/21天）施用CBD，并进行高架T-迷宫（ETM）。我们还研究了CBD对ETM的作用是否依赖于DPAG中5-HT 1A介导的神经传递的促进作用。为了后者的目的，我们验证了这些影响是否会被阻止内DPAG注射的5-HT 1A受体拮抗剂WAY 100635（0.37 nmol/0.2 μ L）。此外，我们验证，通过体内微透析，如果CBD慢性治疗增加5-羟色胺（5-HT）的释放，并通过定量聚合酶链反应，如果有变化，在DPAG. Results的5 HT-1A或5 HT-2C mRNA的表达表明，重复，但不是急性外周给药的CBD减少ETM的逃避反应，这表明恐慌的影响。该处理不改变5-HT-1A或5-HT-2C受体mRNA表达，也不改变DPAG中5-羟色胺细胞外浓度。CBD的作用可以通过DPAG注射5-HT 1A受体拮抗剂来阻止。总之，这些发现表明，CBD的重复治疗通过作用于DPAG中的5-HT 1A受体来诱导抗恐慌作用。
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 mu L). 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.