Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 2120, USA.
Psychopharmacology (Berl). 2011 Sep;217(2):189-97. doi: 10.1007/s00213-011-2275-7. Epub 2011 Apr 27.
Endocannabinoids have been widely studied in the context of addiction and reward due to their role in reinstatement. However, little is known about the role of CB1 receptors during extinction learning of an appetitively motivated task.
The aim of this study was to evaluate the role of endocannabinoids at different stages of extinction learning.
Endocannabinoid signaling was disrupted by injecting the CB1 receptor antagonist rimonabant (0, 200, 300 μg/kg i.v.) during the acquisition or consolidation phases of learning. The rate of extinction and its half-life were analyzed, as well as food-seeking in a reward-induced reinstatement test. We further investigated the interaction between extinction and endocannabinoids in different groups of rats that received drug treatments but did not undergo extinction training (abstinence). In addition, the effects of rimonabant on cue retrieval were investigated in a cue-induced reinstatement test in which rimonabant (0, 300 μg/kg i.v.) was given immediately prior to the reinstatement session.
Blockade of CB1 receptors during acquisition or consolidation of extinction learning had no effect on the rate extinction or its half-life and these pretreatments had no long term consequences on reward-seeking behavior. Furthermore, rats that underwent extinction training responded at lower levels than those that received the drug in the absence of extinction (p = 0.000, η (2) = 0.40). Rimonabant was effective in inhibiting behavior only if it was immediately given before a cue-induced reinstatement session (p = 0.000, η (2) = 0.92).
The present results clarify and isolate the role of endocannabinoids in reinstatement as key mediators of cue retrieval, rather than orchestrators of extinction learning processes.
内源性大麻素在成瘾和奖励方面的研究很广泛，这是由于它们在复燃中的作用。然而，在食欲动机任务的消退学习过程中，关于 CB1 受体的作用知之甚少。
本研究旨在评估内源性大麻素在消退学习不同阶段的作用。
通过在学习的获得或巩固阶段静脉注射 CB1 受体拮抗剂利莫那班（0、200、300μg/kg）来破坏内源性大麻素信号。分析了消退的速度及其半衰期，以及在奖励诱导的复燃测试中的食物寻求。我们进一步研究了在接受药物治疗但未进行消退训练（禁欲）的不同大鼠组中，消退和内源性大麻素之间的相互作用。此外，在线索诱导的复燃测试中，在复燃阶段之前立即给予利莫那班（0、300μg/kg 静脉注射），研究了利莫那班对线索检索的影响。
在消退的获得或巩固阶段阻断 CB1 受体对消退的速度或半衰期没有影响，这些预处理对奖励寻求行为没有长期影响。此外，接受消退训练的大鼠的反应水平低于未接受消退训练而接受药物治疗的大鼠（p=0.000，η2=0.40）。只有在立即给予线索诱导的复燃测试之前，利莫那班才会有效抑制行为（p=0.000，η2=0.92）。
本研究结果阐明并分离了内源性大麻素在复燃中的作用，作为线索检索的关键介质，而不是消退学习过程的协调者。
