引用

我们最近建立了一个大鼠模型，在食物选择诱导的自愿戒断后复发到药物寻求。我们用这个模型来研究眼窝额叶皮层(OFC)及其传入投射在芬太尼寻求复发中的作用。我们训练雄性和雌性大鼠自我给药6天(6-h/天)和静脉注射芬太尼(2.5 g/kg/滴注)12天(6-h/天)。通过芬太尼注射和美味食物之间的离散选择程序(20次/天)，我们评估了13-14天自愿戒酒后芬太尼寻求复发。在两性中，食物选择诱导的禁欲后的复发与OFC中活动标记物Fos的表达增加有关。肌西摩尔+巴氯芬(50+50 ng/侧)灭活OFC降低芬太尼复发。然后，我们通过使用Fos和逆行示踪剂霍乱毒素B(注射到OFC中)在复发试验中确定OFC传入的投射特异性激活。芬太尼寻求复发与投射到OFC的梨状皮层(Pir)神经元Fos表达增加有关，但在基底外侧杏仁核和丘脑的投射中没有。肌西摩尔+巴氯芬对Pir的药理失活降低了自愿戒断后寻求芬太尼的复发。接下来，我们使用解剖分离程序来确定Pir和OFC之间的投影是否对芬太尼寻求复发至关重要。 Unilateral muscimol+baclofen injections into Pir in one hemisphere plus unilateral muscimol+baclofen injections into OFC in the contralateral but not ipsilateral hemisphere decreased relapse. Our results identify Pir-OFC projections as a new motivation-related pathway critical to relapse to opioid seeking after voluntary abstinence.SIGNIFICANCE STATEMENTThere are few preclinical studies of fentanyl relapse and these studies have used experimenter-imposed extinction or forced abstinence procedures. In humans, however, abstinence is often voluntary, with drug available in the drug environment but forgone in favor of non-drug alternative reinforcers. We recently developed a rat model of drug relapse after palatable food choice-induced voluntary abstinence. Here we used classical pharmacology, immunohistochemistry, and retrograde tracing to demonstrate a critical role of the piriform and orbitofrontal cortices in relapse to opioid seeking after voluntary abstinence. Copyright 2020 the authors.