Lifetime relapse rates remain a major obstacle in addressing the current opioid crisis. Relapse to opioid use can be modeled in rodent studies where drug self-administration is followed by a period of abstinence and a subsequent test for drug seeking. Abstinence can be achieved through extinction training, forced abstinence, or voluntary abstinence. Voluntary abstinence can be accomplished by introducing adverse consequences of continued drug self-administration (e.g., punishment or electric barrier) or by introducing an alternative nondrug reward in a discrete choice procedure (drug versus palatable food or social interaction). In this review, we first discuss pharmacological and circuit mechanisms of opioid seeking, as assessed in the classical extinction-reinstatement model, where reinstatement is induced by reexposure to the self-administered drug (drug priming), discrete cues, discriminative cues, drug-associated contexts, different forms of stress, or withdrawal states. Next, we discuss pharmacological and circuit mechanisms of relapse after forced or voluntary abstinence, including the phenomenon of "incubation of heroin craving" (the time-dependent increases in heroin seeking during abstinence). We conclude by discussing future directions of preclinical relapse-related studies using opioid drugs.

中文翻译：

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在大鼠模型中复发至阿片类药物搜寻：行为，药理和回路。

终生复发率仍然是解决当前阿片类药物危机的主要障碍。可以在啮齿动物研究中对阿片类药物的复发进行建模，在该研究中，药物的自我给药，禁欲期和随后的药物寻找测试将被模拟。节制可以通过灭绝训练，强迫性节制或自愿性节制来实现。自愿戒酒可以通过引入持续的药物自我管理带来的不利后果（例如，惩罚或电障碍）或通过在离散选择程序（药物与可口食品或社交互动）中引入替代性非药物奖励来实现。在这篇综述中，我们首先讨论了在经典的灭绝恢复模型中评估的阿片类药物的药理和回路机制，暴露于自我管理的药物（药物引发），离散线索，判别线索，与药物相关的环境，不同形式的压力或戒断状态引起的恢复。接下来，我们讨论强迫或自愿戒酒后复发的药理和回路机制，包括“海洛因渴望孵化”现象（禁欲期间海洛因搜寻的时间依赖性增加）。我们通过讨论使用阿片类药物的临床前复发相关研究的未来方向作为总结。（禁欲期间海洛因搜寻的时间依赖性增加）。我们通过讨论使用阿片类药物的临床前复发相关研究的未来方向作为总结。（禁欲期间海洛因搜寻的时间依赖性增加）。我们通过讨论使用阿片类药物的临床前复发相关研究的未来方向作为总结。