Neuronal Ensembles in Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Neurobiology of Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, United States.
Elife. 2019 Feb 25;8:e44427. doi: 10.7554/eLife.44427.
In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency ('') over time. Animal models of incubation may help develop treatments to prevent relapse, but these models have ubiquitously focused on the role of conditioned stimuli (CSs) signaling drug delivery. Discriminative stimuli (DSs) are unique in that they exert stimulus-control over both drug taking and drug seeking behavior and are difficult to extinguish. For this reason, incubation of the excitatory effects of DSs that signal drug availability, not yet examined in preclinical studies, could be relevant to relapse prevention. We trained rats to self-administer cocaine (or palatable food) under DS control, then investigated DS-controlled incubation of craving, in the absence of drug-paired CSs. DS-controlled cocaine (but not palatable food) seeking incubated over 60 days of abstinence and persisted up to 300 days. Understanding the neural mechanisms of this DS-controlled incubation holds promise for drug relapse treatments.
在戒除毒瘾的吸毒者中，与吸毒经历相关的线索随着时间的推移会获得引发复吸的能力（“”）。孵育的动物模型可能有助于开发预防复吸的治疗方法，但这些模型普遍侧重于条件刺激（CSs）信号传递药物的作用。辨别刺激（DSs）的独特之处在于，它们对药物摄取和药物寻求行为都具有刺激控制作用，并且难以消除。出于这个原因，尚未在临床前研究中检查过的信号药物可用性的 DSs 的兴奋性效应的孵育可能与预防复发有关。我们训练大鼠在 DS 控制下自行摄入可卡因（或美味食物），然后在没有药物配对 CSs 的情况下研究 DS 控制下的渴望孵育。DS 控制下的可卡因（但不是美味食物）寻求在 60 天的禁欲期内孵育，并持续长达 300 天。了解这种 DS 控制孵育的神经机制有望为药物复发治疗提供帮助。
