Withdrawal from Δ⁹-tetrahyrocannibidol (THC) is associated with a host of dysphoric symptoms that increase probability of relapse. To date, many animal models of THC withdrawal rely on withdrawal-induced somatic withdrawal signs leaving withdrawal-suppressed behavior relatively unexplored. As compared with withdrawal-induced behaviors, ongoing behavior that is suppressed by withdrawal is a useful behavioral endpoint because it 1) more effectively models the subjective aspects of withdrawal and 2) identifies pharmacotherapies that restore behavior to baseline levels, rather than eliminate behavior induced by withdrawal. The current study assessed effects of spontaneous and rimonabant-precipitated THC withdrawal in mice responding on a progressive-ratio (PR) schedule of sucrose water reinforcement. Once behavior stabilized, male and female mice were administered THC (10 mg/kg, s.c.) or vehicle for five or six days. THC was either discontinued and behavior monitored for three days during abstinence, or the CB₁ antagonist rimonabant (2 mg/kg, i.p.) was used to precipitate withdrawal. Whereas spontaneous THC withdrawal had no effect on PR performance, THC-treated mice were differentially sensitive to rimonabant administration via large decreases in break point, overall response rate, and run rate relative to vehicle-treated mice. Importantly, pretreatment with the CB₁ positive allosteric modulator ZCZ011 (10 mg/kg, i.p.) did not prevent precipitated-withdrawal-induced behavioral impairment. These extend findings of earlier studies suggesting operant baselines are useful tools to study subjective effects of cannabinoid withdrawal. Additionally, operant baselines allow withdrawal pharmacotherapies to be tested in a restoration-of-function context, which may be more sensitive, selective, and clinically relevant.

戒断 Δ ⁹ -四氢卡尼比多 (THC) 会导致一系列烦躁症状，从而增加复发的可能性。迄今为止，许多 THC 戒断动物模型依赖于戒断引起的躯体戒断症状，​​而对戒断抑制行为的研究相对较少。与戒断诱发的行为相比，被戒断抑制的持续行为是一个有用的行为终点，因为它 1）更有效地模拟戒断的主观方面，2）确定将行为恢复到基线水平的药物疗法，而不是消除戒断诱发的行为。撤回。目前的研究评估了小鼠自发和利莫那班沉淀 THC 戒断对蔗糖水强化渐进比例 (PR) 方案的影响。一旦行为稳定，雄性和雌性小鼠就被给予 THC（10 毫克/千克，皮下）或载体五到六天。要么停用THC，并在禁欲期间监测行为三天，要么使用CB ₁拮抗剂利莫那班（2 mg/kg，腹膜内注射）来促进戒断。虽然自发 THC 戒断对 PR 表现没有影响，但 THC 治疗的小鼠对利莫那班给药的敏感性不同，相对于媒介物治疗的小鼠，断点、总体反应率和运行率大幅降低。重要的是，用CB ₁正变构调节剂ZCZ011（10 mg/kg，腹腔注射）进行预处理并不能预防突然戒断引起的行为障碍。这些扩展了早期研究的结果，表明操作基线是研究大麻素戒断主观影响的有用工具。 此外，操作性基线允许在功能恢复的背景下测试戒断药物疗法，这可能更敏感、更具选择性和临床相关性。