探究在信号和目标追踪大鼠的冲突性戒断后，阿片类药物寻求的辨别性刺激调节。
Investigating discriminative stimulus modulation of opioid seeking after conflict-induced abstinence in sign- and goal-tracking rats.
机构信息
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD, 21201, USA.
出版信息
Psychopharmacology (Berl). 2022 Oct;239(10):3223-3236. doi: 10.1007/s00213-022-06204-7. Epub 2022 Aug 16.
RATIONALE
Discriminative stimuli (DS) are cues that predict reward availability. DS are resistant to extinction and motivate drug seeking even after long periods of abstinence. Previous studies have demonstrated that sign-tracking (ST) and goal-tracking (GT) differences in Pavlovian approach predict distinct cue-modulated vulnerabilities to cocaine reinstatement. GT rats show heightened reinstatement to contextual and DS, while ST rats show heightened reinstatement to discrete stimuli. Here we examine whether DS modulate reinstatement after electric barrier-induced abstinence and whether tracking-related relapse vulnerabilities generalize to opioid relapse.
OBJECTIVES
We examine whether DS-modulated reinstatement to fentanyl seeking persists in the presence of reduced adverse consequences after electric barrier-induced abstinence. We also examine whether tracking differences predict the magnitude of DS-modulated reinstatement of fentanyl seeking after electric barrier-induced abstinence.
METHODS
We used Pavlovian lever autoshaping (PLA) training to determine sign-, goal-, and intermediate tracking groups in male and female Sprague Dawley rats. We then trained rats in a DS model of intermittent fentanyl self-administration, and extinguished drug seeking by imposing an electric barrier of increasing intensity. We then measured the level of DS-modulated reinstatement in the presence of a reduced electric barrier intensity.
RESULTS
We report that DS strongly modulate fentanyl seeking after electric barrier-induced abstinence. DS-modulation of fentanyl acquisition, electric barrier-induced abstinence, and reinstatement was similar for sign- and goal-tracking groups.
CONCLUSIONS
Discriminative stimuli powerfully motivate opioid seeking, despite continued aversive consequences. Pavlovian approach differences do not predict the level of DS-modulated reinstatement to fentanyl seeking after conflict-induced abstinence.
原理
辨别刺激（DS）是预测奖励可用性的线索。DS 不易被消除，即使在长时间的禁欲后，也能激发药物寻求。先前的研究表明，在 Pavlovian 接近过程中，信号跟踪（ST）和目标跟踪（GT）的差异预测了可卡因复吸的不同线索调节脆弱性。GT 大鼠表现出对上下文和 DS 的增强复吸，而 ST 大鼠表现出对离散刺激的增强复吸。在这里，我们研究了在电障碍引起的禁欲后，DS 是否调节复吸，以及与跟踪相关的复发脆弱性是否推广到阿片类药物的复发。
目的
我们研究了在电障碍引起的禁欲后，减少不良后果的情况下，DS 调节芬太尼寻求的复吸是否仍然存在。我们还研究了跟踪差异是否预测了电障碍引起的禁欲后，DS 调节芬太尼寻求的复吸的幅度。
方法
我们使用 Pavlovian 杠杆自动塑造（PLA）训练来确定雄性和雌性 Sprague Dawley 大鼠的信号、目标和中间跟踪组。然后，我们在间歇性芬太尼自我给药的 DS 模型中训练大鼠，并通过施加强度逐渐增加的电障碍来消除药物寻求。然后，我们在降低电障碍强度的情况下测量 DS 调节的复吸水平。
结果
我们报告说，DS 在电障碍引起的禁欲后强烈调节芬太尼的寻求。DS 对芬太尼获取、电障碍引起的禁欲和复吸的调节，在信号和目标跟踪组中是相似的。
结论
尽管持续存在不良后果，但辨别刺激有力地激发了阿片类药物的寻求。在冲突引起的禁欲后，Pavlovian 接近差异不能预测 DS 调节的芬太尼寻求复吸的水平。
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