Section of Cagliari, Neuroscience Institute, National Research Council of Italy, Monserrato, Italy.
Cagliari Pharmacological Research s.r.l., Cagliari, Italy.
Cannabis Cannabinoid Res. 2022 Apr;7(2):161-169. doi: 10.1089/can.2020.0132. Epub 2021 Mar 11.
Cannabidiol (CBD) is a major cannabinoid extracted from with no abuse potential. Data from recent rodent studies suggest that amelioration of alcohol-motivated behaviors may be one of the numerous pharmacological effects of CBD. This study was designed to contribute to this research, assessing the effect of CBD on operant oral alcohol self-administration in selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive alcohol consumption. In addition, this study investigated the effect of CBD on operant self-administration of a highly palatable chocolate solution in Wistar rats. Male sP rats were trained to lever respond for alcohol (15% v/v) under the fixed ratio 4 (FR4) schedule of reinforcement. Once lever responding had stabilized, rats were exposed to test sessions under the FR4 and progressive ratio (PR) schedules of reinforcement. Test sessions were preceded by acute treatment with CBD (0, 6.25, 12.5, and 25 mg/kg or 0, 25, 50, and 100 mg/kg, i.p.; each dose range was tested in an independent experiment). Male Wistar rats were trained to lever respond for a chocolate solution (5% w/v chocolate powder) under the FR10 schedule of reinforcement. Once lever responding had stabilized, rats were exposed to test sessions under the same schedule. Test sessions were preceded by acute treatment with CBD (0, 6.25, 12.5, and 25 mg/kg or 0, 25, 50, and 100 mg/kg, i.p., in two independent experiments). Under the FR schedule, treatment with doses of CBD ≥12.5 mg/kg markedly reduced lever responding for alcohol and amount of self-administered alcohol. Under the PR schedule, treatment with CBD produced a slight tendency toward a decrease in lever responding and breakpoint for alcohol. Finally, no dose of CBD affected lever responding for the chocolate solution and amount of self-administered chocolate solution. These results extend previous data on CBD ability to affect alcohol-motivated behaviors to an animal model of genetically-determined proclivity to high alcohol consumption. Because of the predictive validity of sP rats, these results may be of relevance in view of possible future studies testing CBD in patients affected by alcohol use disorder.
大麻二酚（CBD）是一种主要的大麻素，从大麻中提取，没有滥用的潜力。最近的啮齿动物研究数据表明，改善酒精动机行为可能是 CBD 的众多药理学作用之一。本研究旨在为此项研究做出贡献，评估 CBD 对选择性繁殖的撒丁岛酒精偏好（sP）大鼠的操作性口服酒精自我给药的影响，这是一种过度饮酒的验证动物模型。此外，本研究还研究了 CBD 对 Wistar 大鼠操作性自我给药高可口巧克力溶液的影响。雄性 sP 大鼠接受训练，以在固定比例 4（FR4）强化方案下对酒精（15% v/v）进行杠杆反应。一旦杠杆反应稳定，大鼠就会在 FR4 和递增比例（PR）强化方案下进行测试。测试前，大鼠接受急性 CBD 治疗（0、6.25、12.5 和 25mg/kg 或 0、25、50 和 100mg/kg，ip；每个剂量范围在一个独立的实验中进行测试）。雄性 Wistar 大鼠接受训练，以在 FR10 强化方案下对巧克力溶液（5% w/v 巧克力粉）进行杠杆反应。一旦杠杆反应稳定，大鼠就会在相同的方案下进行测试。测试前，大鼠接受急性 CBD 治疗（0、6.25、12.5 和 25mg/kg 或 0、25、50 和 100mg/kg，ip，在两个独立的实验中进行）。在 FR 方案下，剂量≥12.5mg/kg 的 CBD 治疗显著减少了酒精的杠杆反应和自我给药的酒精量。在 PR 方案下，CBD 治疗产生了轻微降低酒精杠杆反应和断点的趋势。最后，没有剂量的 CBD 影响巧克力溶液的杠杆反应和自我给药的巧克力溶液量。这些结果将 CBD 影响酒精动机行为的能力扩展到一种遗传上倾向于高酒精消费的动物模型。由于 sP 大鼠的预测有效性，鉴于可能对患有酒精使用障碍的患者进行 CBD 测试的未来研究，这些结果可能具有相关性。
