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.

与植物来源的 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严重的戒断症状。避免戒断症状，​​包括致焦虑作用，有助于继续使用大麻素。成年雄性和雌性 Long-Evans 大鼠通过每天两次颈内输注逐渐增加剂量的 WIN 55,212-2 (WIN)。最后一次输注后 4 小时用 SR 141716（利莫那班）诱发突然戒断。通过将 30 分钟内观察到的躯体行为的 z 分数与通过束断同时收集的运动活动相加来编制全局戒断分数 (GWS) 。利莫那班分别在 3 mg/kg 和 10 mg/kg 剂量下促使雌性和雄性大鼠戒断，但导致 GWS 的个体行为并不相同。3 mg/kg 利莫那班不影响女性的运动行为，但 10 mg/kg 利莫那班会降低男性对照的运动行为。最后一次输注后 6 至 96 小时内观察到的自发戒断可在 WIN 给药后 24 小时内进行量化。影响 GWS 的个人行为因性别和时间点而异。经历自发戒断的男性比经历戒断的女性进行更多的运动。在 WIN 或载体输注后一到两周，对不同组的大鼠进行一系列类似焦虑的行为测试（高架十字迷宫、开放场地测试和大理石埋藏测试）。禁欲一周后，在大理石埋葬和露天测试中发现了与性相关的影响，但与药物治疗无关。禁欲两周后，与男性相比，经历戒断的女性在大理石埋葬过程中花费了更多的时间梳理毛发，并进行了更多的大理石操作。WIN 输注不会影响动情周期，并且 GWS 评分与停药时的动情不相关。总的来说，这些结果显示了行为上的定性性别差异，导致了大麻素戒断的行为体验，支持了 THC 的临床发现。