Repeated Cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus
Repeated Cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus
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DOI：
10.1016/j.neuropharm.2018.09.043
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发表时间：
2018-12-01
影响因子：
4.7
通讯作者：
Valverde, Olga
中科院分区：
文献类型：
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作者：
Angel Lujan, Miguel;Castro-Zavala, Adriana;Valverde, Olga
大麻素衍生物在治疗包括药物成瘾在内的神经精神疾病方面显示出有希望的结果。最近关于大麻二酚（CBD）对药物滥用的治疗作用的研究显示出不同的结果，特别是与可卡因等精神兴奋剂物质。为了确定CBD是否可以减弱可卡因强化，我们使用行为致敏、条件位置偏好和静脉给药范式评估了可卡因诱导小鼠的行为反应。我们发现，重复使用CBD可以在升高+迷宫测试中产生焦虑作用，增加新物体识别任务的辨别指数，减弱可卡因诱导的条件位置偏好，但不影响行为敏化。在自我给药范式中，CBD降低了可卡因自愿消费和递进比率断点，但没有药物诱导的恢复。同时，CBD增加海马中1型大麻素受体的表达、MAPK-CREB磷酸化、BDNF表达和神经细胞增殖，降低纹状体中GluA1/2 AMPA亚单位受体比例。总之，我们表明CBD可以调节可卡因强化的一些行为和分子表现。此外，我们的研究结果表明，CBD对吸食可卡因的动物也有促进神经发生的作用。总的来说，这一新证据为使用CBD作为治疗工具提供了新的视角。
Cannabinoid derivatives have shown promising results for treating neuropsychiatric disorders, including drug addiction. Recent studies on the therapeutic effects of Cannabidiol (CBD) on drug abuse showed mixed results, especially with psychostimulant substances such as cocaine. To determine whether CBD can attenuate cocaine reinforcement, we assessed behavioural responses induced by cocaine in mice, using the behavioural sensitization, conditioned place preference and intravenous self-administration paradigms. We show that repeated CBD treatment produces anxiolytic effects in the elevated plus maze test, increases the discrimination index of the novel object recognition task and attenuates cocaine-induced conditioned place preference but does not affect behavioural sensitization. CBD reduced cocaine voluntary consumption and progressive ratio breaking point in the self-administration paradigm, but not drug-induced reinstatement. In parallel, CBD increased expression of type 1 cannabinoid receptor, MAPK-CREB phosphorylation, BDNF expression, and neural cell proliferation in the hippocampus, and reduced the GluA1/2 AMPA subunit receptor ratio in the striatum. In summary, we show that CBD can modulate some behavioural and molecular manifestations of cocaine reinforcement. Moreover, our findings show that CBD has pro-neurogenic effects also in cocaine consuming animals. Overall, this novel evidence provides new perspectives to use CBD as a therapeutic tool.