Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release
Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release
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DOI：
10.1016/j.neuro.2015.08.007
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发表时间：
2015-09-01
期刊：
影响因子：
3.4
通讯作者：
Moreira, Fabricio A.
中科院分区：
文献类型：
--
作者：
Gobira, Pedro H.;Vilela, Luciano R.;Moreira, Fabricio A.
大麻二酚 (CBD) 是大麻的主要非拟精神病成分，具有治疗某些精神和神经系统疾病的潜力。实验动物研究和有限的人体试验表明 CBD 具有抗惊厥和神经保护特性。然而，其对可卡因神经毒性的作用仍不清楚。因此，本研究检验了 CBD 可以预防可卡因引起的癫痫发作的假设，并调查了其潜在机制。 CBD (30 mg/kg) 预处理增加了可卡因 (75 mg/kg) 引起的小鼠癫痫发作的潜伏期并缩短了持续时间。 CBI 受体拮抗剂 AM251（1 和 3 mg/kg）和 CB2 受体拮抗剂 AM630（2 和 4 mg/kg）未能逆转这种保护作用，表明存在替代机制。对接受药物治疗的动物海马体进行的突触体研究表明，可卡因会增加谷氨酸的释放，而 CBD 则会产生相反的效果。最后，这种大麻素对可卡因诱导的癫痫发作的保护作用被雷帕霉素（1 和 5 毫克/千克）逆转，雷帕霉素是哺乳动物雷帕霉素靶点 (mTOR) 细胞内途径的抑制剂。总之，CBD 可防止可卡因中毒模型中的癫痫发作。这些效应可能是通过激活 mTOR 并随后减少谷氨酸释放而发生的。应进一步研究 CBD 作为减轻精神兴奋剂毒性的策略。 (C) 2015 Elsevier Inc. 保留所有权利。
Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders. Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties. Its effects against cocaine neurotoxicity, however, have remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms. CBD (30 mg/kg) pre-treatment increased the latency and reduced the duration of cocaine (75 mg/kg)-induced seizures in mice. The CBI receptor antagonist, AM251 (1 and 3 mg/kg), and the CB2 receptor antagonist, AM630 (2 and 4 mg/kg), failed to reverse this protective effect, suggesting that alternative mechanisms are involved. Synaptosome studies with the hippocampus of drug-treated animals revealed that cocaine increases glutamate release, whereas CBD induces the opposite effect. Finally, the protective effect of this cannabinoid against cocaine-induced seizure was reversed by rapamycin (1 and 5 mg/kg), an inhibitor of the mammalian target of rapamycin (mTOR) intracellular pathway. In conclusion, CBD protects against seizures in a model of cocaine intoxication. These effects possibly occur through activation of mTOR with subsequent reduction in glutamate release. CBD should be further investigated as a strategy for alleviating psychostimulant toxicity. (C) 2015 Elsevier Inc. All rights reserved.