Lennon Veronica A, Brenner Megan B, Weber Sophia J, Komer Lauren E, Madangopal Rajtarun
Neuronal Ensembles in Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States.
Bio Protoc. 2019 Dec 5;9(23):e3445. doi: 10.21769/BioProtoc.3445.
In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency ('') over time. Animal models of incubation may help in developing treatments for relapse prevention. However, these models have primarily focused on the role of conditioned stimuli (CSs) signaling drug delivery and not on discriminative stimuli (DSs), which signal drug availability and are also known to play a major role in drug relapse. We recently showed that DS-controlled cocaine seeking in rats also incubates during abstinence and persists up to 300 days. We used a trial-based procedure to train male and female rats to discriminate between two light cues: one light cue (DS+) signaled the availability of cocaine reward and the second light cue (DS-) signaled the absence of reward. Rats learned to press a central retractable lever during trials in which the DS+ cue was presented and to suppress responding when the DS- cue was presented. Here, we provide a detailed protocol for the behavioral procedure used in our study. The trial-based design of this behavior lends itself well to time-locked recording and manipulation approaches that can be used to identify neurobiological mechanisms underlying the contributions of DSs to drug relapse.
在戒毒的药物成瘾者中，曾经与吸毒经历相关的线索会随着时间的推移而获得诱发复吸的效力。潜伏的动物模型可能有助于开发预防复吸的治疗方法。然而，这些模型主要关注的是信号传递药物给药的条件刺激（CSs）的作用，而不是辨别刺激（DSs），辨别刺激信号药物的可获得性，并且已知在药物复吸中也起主要作用。我们最近表明，大鼠中由辨别刺激控制的可卡因觅求行为在戒断期间也会潜伏，并持续长达300天。我们使用基于试验的程序训练雄性和雌性大鼠区分两种光线索：一种光线索（DS+）表示可获得可卡因奖励，另一种光线索（DS-）表示无奖励。大鼠学会在呈现DS+线索的试验期间按压中央可伸缩杠杆，并在呈现DS-线索时抑制反应。在这里，我们提供了我们研究中使用的行为程序的详细方案。这种行为的基于试验的设计非常适合用于时间锁定记录和操纵方法，这些方法可用于识别辨别刺激对药物复吸的贡献背后的神经生物学机制。
