In addition to overt somatic symptoms, cannabinoid withdrawal can also manifest as disruptions in motivation and attention. Experimental animal models using operant-conditioning approaches reveal these differences, in either antagonist-precipitated or spontaneous withdrawal models. However, these processes have yet to be characterized in the same subjects simultaneously. To differentiate between motivational and attentional processes disrupted in cannabinoid withdrawal, the current study used a response alternation task in which a fixed-ratio (FR) schedule repeatedly alternated between two spatially distinct response options throughout daily training sessions. This task yielded traditional measures of motivation (e.g., response latency) as well as attention (e.g., responses to the incorrect side). After two weeks of training, male and female C57BL/6 J mice either received vehicle or Δ⁹-THC (10 mg/kg, s.c.) twice daily for 5 days. On the 6th day, all mice received their final injection of vehicle or Δ⁹-THC followed 30 min later by injection of the CB₁ receptor selective inverse agonist rimonabant (2 mg/kg, i.p.) to precipitate withdrawal. Testing continued for 3 days post-rimonabant to assess how THC abstinence impacted task performance. Whereas rimonabant decreased response rates to equal degrees in THC-treated and vehicle-treated mice, THC-treated mice showed longer session times, longer response latencies, and more errors per reinforcer. Only THC-treated mice showed a longer latency to switch after committing an error reflecting that precipitated withdrawal impacted measures of both motivation and attention. During the 3-day abstinence window, performance of vehicle-treated mice returned to baseline, but THC-treated mice continued to show disruptions in motivational measures. Importantly, attentional measures (errors and latency to switch after an error) were unaffected by THC abstinence. These data suggest that precipitated and “spontaneous” cannabinoid withdrawal may be qualitatively and quantitatively distinct withdrawal conditions with precipitated withdrawal disrupting both attentional and motivational processes, while abstinence may only affect motivation.

除了明显的躯体症状外，大麻素戒断还可能表现为动机和注意力的破坏。使用操作性条件反射方法的实验动物模型揭示了拮抗剂诱发或自发戒断模型中的这些差异。然而，这些过程尚未在同一受试者中同时得到表征。为了区分大麻素戒断中扰乱的动机和注意力过程，当前的研究使用了反应交替任务，其中固定比例（FR）计划在整个日常训练课程中在两个空间不同的反应选项之间反复交替。这项任务产生了传统的动机测量（例如，反应延迟）以及注意力（例如，对错误一侧的反应）。训练两周后，雄性和雌性 C57BL/6 J 小鼠每天两次^{接受载体或 Δ 9 -THC（10 mg/kg，皮下注射），持续 5 天。}在第6天，所有小鼠接受最后一次注射载体或Δ ⁹ -THC，30分钟后注射CB ₁受体选择性反向激动剂利莫那班（2 mg/kg，腹膜内）以促进戒断。利莫那班后继续进行 3 天的测试，以评估 THC 戒断如何影响任务表现。虽然利莫那班在 THC 治疗和载体治疗的小鼠中同等程度地降低了反应率，但 THC 治疗的小鼠表现出更长的会话时间、更长的反应潜伏期和每个强化剂的更多错误。只有接受 THC 治疗的小鼠在犯错误后表现出更长的转换潜伏期，这反映出突然的戒断影响了动机和注意力的测量。在 3 天的禁欲窗口期间，接受媒介物治疗的小鼠的表现恢复到基线，但接受 THC 治疗的小鼠继续表现出动机测量的破坏。重要的是，注意力测量（错误和错误后切换的延迟）不受 THC 戒断的影响。这些数据表明，突然的和“自发的”大麻素戒断可能是在质量和数量上不同的戒断条件，突然的戒断会扰乱注意力和动机过程，而戒断可能只会影响动机。