BACKGROUND Drug use causes the formation of strong cue/reward associations which persist long after cessation of drug-taking and contribute to the long-term risk of relapse. Extinguishing these associations may reduce cue-induced craving and relapse. Previously, we found that pairing vagus nerve stimulation (VNS) with extinction of cocaine self-administration reduces cue-induced reinstatement; however, it remains unclear whether this was primarily caused by extinguishing the context, the instrumental response, or both. OBJECTIVE Hypothesis: We hypothesized that VNS can facilitate the extinction of both contextual cues and instrumental responding. METHODS Extinction of context was first tested using Pavlovian conditioned place preference (CPP). Next, the impact of VNS on the extinction of instrumental responding was assessed under ABA and AAA context conditions. In each extinction context separate groups of rats were either provided the opportunity to perform the instrumental response, or the levers were retracted for the duration of extinction training. Reinstatement was induced by reintroduction of the conditioned stimuli and/or the drug-paired context. Data were analyzed using one-way or two-way repeated measures ANOVAs. RESULTS VNS during extinction reduced reinstatement of CPP. VNS also reduced cue- and context-induced reinstatement of the instrumental response under both AAA and ABA conditions. The subjects' ability to engage with the lever during extinction was crucial for this effect. P values < 0.05 were considered significant. CONCLUSIONS Craving occurs in response to a range of conditioned stimuli and contexts; VNS may improve outcomes of behavioral therapy by facilitating extinction of both an instrumental response and/or contextual cues.

中文翻译：

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消退学习过程中的迷走神经刺激可减少条件性位置偏好和情境诱导的可卡因寻求恢复


背景吸毒导致强烈的提示/奖励关联的形成，这种关联在停止吸毒后持续很长时间并导致长期复发风险。消除这些关联可能会减少提示引起的渴望和复发。此前，我们发现将迷走神经刺激（VNS）与可卡因自我消除配对可以减少提示诱导的恢复；然而，目前尚不清楚这是否主要是由于消除背景、仪器反应或两者兼而有之。客观假设：我们假设 VNS 可以促进情境线索和工具反应的消失。方法首先使用巴甫洛夫条件位置偏好（CPP）测试情境消退。接下来，在 ABA 和 AAA 环境条件下评估了 VNS 对仪器响应消失的影响。在每种灭绝背景下，不同组的老鼠要么有机会进行仪器反应，要么在灭绝训练期间收回杠杆。通过重新引入条件刺激和/或药物配对环境来诱导恢复。使用单向或双向重复测量方差分析来分析数据。结果 灭绝期间的 VNS 减少了 CPP 的恢复。 VNS 还减少了 AAA 和 ABA 条件下提示和情境诱导的仪器反应恢复。受试者在灭绝期间与杠杆接触的能力对于这种效果至关重要。 P 值 < 0.05 被认为是显着的。结论 渴望的发生是对一系列条件刺激和环境的反应； VNS 可以通过促进工具反应和/或情境线索的消失来改善行为治疗的结果。