PDF(Pubmed)
Abstract：
Synthetic cannabinoids are associated with higher risk of dependence and more intense withdrawal symptoms than plant-derived Δ9-tetrahydrocannabinol (THC). Avoidance of withdrawal symptoms, including anxiogenic effects, can contribute to continued cannabinoid use. Adult male and female Long-Evans rats were given escalating doses of WIN 55,212-2 (WIN) via twice daily intrajugular infusions. Precipitated withdrawal was elicited with SR 141716 (rimonabant) 4 h after the final infusion. Global withdrawal scores (GWS) were compiled by summing z-scores of observed somatic behaviors over a 30-min period with locomotor activity simultaneously collected via beam breaks. Rimonabant precipitated withdrawal in female and male rats at 3 or 10 mg/kg, respectively, but the individual behaviors contributing to GWS were not identical. 3 mg/kg rimonabant did not impact locomotor behavior in females, but 10 mg/kg decreased locomotion in male controls. Spontaneous withdrawal observed between 6 and 96 h after the final infusion was quantifiable up to 24 h following WIN administration. Individual behaviors contributing to GWS varied by sex and time point. Males undergoing spontaneous withdrawal engaged in more locomotion than females undergoing withdrawal. Separate groups of rats were subjected to a battery of anxiety-like behavioral tests (elevated plus maze, open field test, and marble burying test) one or two weeks after WIN or vehicle infusions. At one week abstinence, sex-related effects were noted in marble burying and the open field test but were unrelated to drug treatment. At two weeks abstinence, females undergoing withdrawal spent more time grooming during marble burying and performed more marble manipulations than their male counterparts. WIN infusions did not impact estrous cycling, and GWS scores were not correlated with estrous at withdrawal. Collectively, these results show qualitative sex differences in behaviors contributing to the behavioral experience of cannabinoid withdrawal supporting clinical findings from THC.
摘要：
与植物衍生的Δ9-四氢大麻酚（THC）相比，合成大麻素具有更高的依赖性风险和更强烈的戒断症状。避免戒断症状，包括焦虑作用，可能有助于继续使用大麻素。成年雄性和雌性Long-Evans大鼠通过每日两次颈内输注给予递增剂量的WIN55,212-2（WIN）。最终输注后4小时，用SR141716（利莫那班）引起沉淀的戒断。通过将30分钟内观察到的躯体行为的z得分与通过束断裂同时收集的运动活动相加，来编制全局退缩得分（GWS）。利莫那班在3或10mg/kg的雌性和雄性大鼠中沉淀戒断，分别,但是导致GWS的个体行为并不相同。3mg/kg利莫那班不影响女性的运动行为，但是10mg/kg降低了男性对照组的运动能力。最终输注后6至96小时之间观察到的自发停药可量化至WIN给药后24小时。导致GWS的个人行为因性别和时间而异。自发退缩的男性比退缩的女性从事更多的运动。分别对大鼠进行了一系列类似焦虑的行为测试（高架加迷宫，露天试验,和大理石掩埋测试）WIN或车辆输注后一到两周。禁欲一周，在大理石掩埋和野外试验中发现了与性别相关的影响，但与药物治疗无关。禁欲两周后，与男性相比，接受戒断的女性在大理石掩埋过程中花费更多的时间进行梳理，并进行更多的大理石操作。WIN输液不会影响动情周期，GWS评分与戒断时的发情期无关。总的来说，这些结果显示了行为方面的定性性别差异,这些差异有助于大麻素戒断的行为体验,支持来自THC的临床发现.
