Investigation of Cannabidiol in the Mouse Drug Discrimination Paradigm.
Investigation of Cannabidiol in the Mouse Drug Discrimination Paradigm.
复制标题
小鼠药物歧视范式中大麻二酚的研究。
DOI：
10.1089/can.2022.0198
复制
发表时间：
2024
影响因子：
3.8
通讯作者：
Lichtman,AronH
中科院分区：
文献类型：
--
作者：
Mustafa,MohammedA;Poklis,JustinL;Karin,KimberlyN;Elmer,JaydenA;Porter,JosephH;Parra,Victoria;Lu,Dai;Schlosburg,JoelE;Lichtman,AronH
大麻二酚（CBD）由于其已知的和潜在的药用特性以及其在广泛产品中的商业成功而获得了相当多的公众和科学关注。虽然CBD在人类中缺乏大麻拟麻醉副作用，并且未能在药物辨别范式的实验室动物模型中取代大麻素1型受体（CB 1 R）激动剂，但轶事报道将其描述为在人类中产生“愉快”的主观效果。因此，我们推测，这种植物大麻素可能会引起不同的主观效果。因此，我们研究了小鼠是否会学会区分CBD和载体。此外，我们研究了CBD是否可以作为一个CB 1 R变构和它是否会提高大脑endocannabinoid concentration.Materials和Methods：C57 BL/6 J小鼠进行了区分训练的CBD或高效率CB 1 R激动剂CP 55，940从车辆。此外，我们研究了CBD或CB 1 R阳性变构调节剂ZCZ 011是否会改变CP 55，940辨别线索。最后，我们测试了急性CBD注射是否会提高内源性大麻素在大脑中的水平，也定量血液和大脑水平的CBD.Results：小鼠未能区分高剂量的CBD从车辆后124天的训练，虽然相同的主题随后获得CP 55，940歧视。在第二组训练辨别CP 55，940的小鼠中，CBD既没有引起替代，也没有改变反应率。单次注射100或200 mg/kg CBD并不影响内源性大麻素和相关脂质的脑水平，并导致血液和全脑中的高药物浓度在0.5小时，并继续增加在3小时。讨论：CBD没有产生内感受性刺激，没有破坏表现在食物驱动的操作性任务，并缺乏明显的有效性改变脑内源性大麻素水平或调节CB 1 R激动剂的药理作用。这些发现支持了CBD缺乏滥用倾向的断言，并且其急性给药似乎在调节整个动物内源性大麻素系统的关键成分方面没有发挥作用。
Introduction:Cannabidiol (CBD) has gained considerable public and scientific attention because of its known and potential medicinal properties, as well as its commercial success in a wide range of products. Although CBD lacks cannabimimetic intoxicating side effects in humans and fails to substitute for cannabinoid type-1 receptor (CB1R) agonists in laboratory animal models of drug discrimination paradigm, anecdotal reports describe it as producing a “pleasant” subjective effect in humans. Thus, we speculated that this phytocannabinoid may elicit distinct subjective effects. Accordingly, we investigated whether mice would learn to discriminate CBD from vehicle. Additionally, we examined whether CBD may act as a CB1R allosteric and whether it would elevate brain endocannabinoid concentrations.Materials and Methods:C57BL/6J mice underwent discrimination training of either CBD or the high-efficacy CB1R agonist CP55,940 from vehicle. Additionally, we examined whether CBD or the CB1R-positive allosteric modulator ZCZ011 would alter the CP55,940 discriminative cue. Finally, we tested whether an acute CBD injection would elevate endocannabinoid levels in brain, and also quantified blood and brain levels of CBD.Results:Mice failed to discriminate high doses of CBD from vehicle following 124 training days, though the same subjects subsequently acquired CP55,940 discrimination. In a second group of mice trained to discriminate CP55,940, CBD neither elicited substitution nor altered response rates. A single injection of 100 or 200 mg/kg CBD did not affect brain levels of endogenous cannabinoids and related lipids and resulted in high drug concentrations in blood and whole brain at 0.5 h and continued to increase at 3 h.Discussion:CBD did not engender an interoceptive stimulus, did not disrupt performance in a food-motivated operant task, and lacked apparent effectiveness in altering brain endocannabinoid levels or modulating the pharmacological effects of a CB1R agonist. These findings support the assertions that CBD lacks abuse liability and its acute administration does not appear to play a functional role in modulating key components of the endocannabinoid system in whole animals.