Opioid use disorder is a chronic relapsing disorder encompassing misuse, dependence, and addiction to opioid drugs. Long term maintenance of associations between the reinforcing effects of the drug and the cues associated with its intake are a leading cause of relapse. Indeed, exposure to the salient drug-associated cues can lead to drug cravings and drug seeking behavior. The dorsal hippocampus (dHPC) and locus coeruleus (LC) have emerged as important structures for linking the subjective rewarding effects of opioids with environmental cues. However, their role in cue-induced reinstatement of opioid use remains to be further elucidated. In this study, we showed that chemogenetic inhibition of excitatory dHPC neurons during re-exposure to drug-associated cues significantly attenuates cue-induced reinstatement of morphine-seeking behavior. In addition, the same manipulation reduced reinstatement of sucrose-seeking behavior but failed to alter memory recall in the object location task. Finally, intact activity of tyrosine hydroxylase (TH) LC-dHPC_Th afferents is necessary to drive cue induced reinstatement of morphine-seeking as inhibition of this pathway blunts cue-induced drug-seeking behavior. Altogether, these studies show an important role of the dHPC and LC-dHPC_Th pathway in mediating cue-induced reinstatement of opioid seeking.

阿片类药物使用障碍是一种慢性复发性疾病，包括阿片类药物的滥用、依赖和成瘾。药物的增强作用和与其摄入相关的线索之间的长期维持关联是复发的主要原因。事实上，暴露于与药物相关的显着线索可能会导致药物渴望和寻求药物的行为。背侧海马 (dHPC) 和蓝斑 (LC) 已成为将阿片类药物的主观奖励效应与环境线索联系起来的重要结构。然而，它们在提示诱导恢复阿片类药物使用中的作用仍有待进一步阐明。在这项研究中，我们发现，在重新暴露于药物相关线索期间，兴奋性 dHPC 神经元的化学遗传学抑制显着减弱了线索诱导的吗啡寻求行为的恢复。此外，相同的操作减少了寻找蔗糖行为的恢复，但未能改变物体定位任务中的记忆回忆。最后，酪氨酸羟化酶 (TH) LC-dHPC _Th传入神经的完整活性对于驱动线索诱导的吗啡寻求恢复是必要的，因为抑制该途径会减弱线索诱导的药物寻求行为。总之，这些研究表明 dHPC 和 LC-dHPC _Th通路在介导线索诱导的阿片类药物寻求恢复中发挥着重要作用。