The anterior cingulate cortex (ACC) is implicated in many pathologies, including depression, anxiety, substance-use disorders, and pain. There is also evidence from brain imaging that the ACC is hyperactive during periods of opioid withdrawal. However, there are limited data contributing to our understanding of ACC function at the cellular level during opioid withdrawal. Here, we address this issue by performing ex vivo electrophysiological analysis of thick-tufted, putative dopamine D2 receptor expressing, layer V pyramidal neurons in the ACC (ACC L5 PyNs) in a mouse model of spontaneous opioid withdrawal. We found that escalating doses of morphine (20, 40, 60, 80, and 100 mg/kg, i.p. on days 1–5, respectively) injected twice daily into male C57BL/6 mice evoked withdrawal behaviors and an associated withdrawal-induced mechanical hypersensitivity. Brain slices prepared 24 h following the last morphine injection showed increases in ACC L5 thick-tufted PyN-intrinsic membrane excitability, increases in membrane resistance, reductions in the rheobase, and reductions in HCN channel-mediated currents (I_H). We did not observe changes in intrinsic or synaptic properties on thin-tufted, dopamine D1-receptor-expressing ACC L5 PyNs recorded from male Drd1a-tdTomato transgenic mice. In addition, we found that chemogenetic inhibition of the ACC blocked opioid-induced withdrawal and withdrawal-induced mechanical hypersensitivity. These results demonstrate that spontaneous opioid withdrawal alters neuronal properties within the ACC and that ACC activity is necessary to control behaviors associated with opioid withdrawal and withdrawal-induced mechanical hypersensitivity. The ability of the ACC to regulate both withdrawal behaviors and withdrawal-induced mechanical hypersensitivity suggests overlapping mechanisms between two seemingly distinguishable behaviors. This commonality potentially suggests that the ACC is a locus for multiple withdrawal symptoms.

前扣带皮层 (ACC) 涉及许多病理，包括抑郁、焦虑、物质使用障碍和疼痛。大脑成像也有证据表明，在阿片类药物戒断期间，ACC 过度活跃。然而，有助于我们了解阿片类药物戒断期间细胞水平的 ACC 功能的数据有限。在这里，我们通过在自发阿片类药物戒断小鼠模型中对 ACC (ACC L5 PyNs) 中厚簇状、推定的多巴胺 D2 受体表达、V 层锥体神经元进行离体电生理分析来解决这个问题。我们发现每天两次向雄性 C57BL/6 小鼠注射剂量递增的吗啡（分别为 20、40、60、80 和 100 mg/kg，腹腔注射，分别在第 1-5 天）会诱发戒断行为和相关的戒断诱发机械反应超敏反应。我_H）。我们没有观察到从雄性Drd1a记录的薄簇状多巴胺 D1 受体表达 ACC L5 PyN 的内在或突触特性的变化-tdTomato 转基因小鼠。此外，我们发现 ACC 的化学遗传学抑制阻断了阿片类药物诱导的戒断和戒断诱导的机械超敏反应。这些结果表明，自发的阿片类药物戒断会改变 ACC 内的神经元特性，并且 ACC 活动对于控制与阿片类药物戒断和戒断诱发的机械超敏反应相关的行为是必要的。ACC 调节戒断行为和戒断引起的机械超敏反应的能力表明两种看似不同的行为之间存在重叠机制。这种共性可能表明 ACC 是多种戒断症状的发源地。