Institute of Neuroscience-Cagliari, CNR National Research Council of Italy, Cagliari, Italy.
Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Cagliari, Italy.
Methods Mol Biol. 2021;2201:231-245. doi: 10.1007/978-1-0716-0884-5_21.
The inability to maintain drug abstinence is often referred to as relapse and consists of a process by which an abstaining individual slips back into old behavioral patterns and substance use. Animal models of relapse have been developed over the last decades and significantly contributed to shed light on the neurobiological mechanisms underlying vulnerability to relapse. The most common procedure to study drug-seeking and relapse-like behavior in animals is the "extinction-reinstatement model." Originally elaborated by Pavlov and Skinner, the concepts of reinforced operant responding were applied to addiction research not before 1971 (Stretch et al., Can J Physiol Pharmacol 49:581-589, 1971), and the first report of a reinstatement animal model as it is now used worldwide was published only 10 years later (De Wit and Stewart, Psychopharmacology 75:134-143, 1981). According to the proposed model, opioids are typically self-administered intravenously, as humans do, and although rodents are most often employed in these studies, a variety of species including nonhuman primates, dogs, cats, and pigeons can be used. Several operant responses are available, depending on the species studied. For example, a lever press or a nose poke response typically is used for rodents, whereas a panel press response typically is used for nonhuman primates. In this chapter we describe a simple and easily reproducible protocol of heroin-seeking reinstatement in rats, which proved useful to study the neurobiological mechanisms underlying relapse to heroin and vulnerability factors enhancing the resumption of heroin-seeking behavior.
无法保持戒毒状态通常被称为复发，包括一个个体重新陷入旧的行为模式和物质使用的过程。在过去几十年中，已经开发出了动物复发模型，这些模型极大地促进了对复发易感性的神经生物学机制的研究。研究动物觅药和类似复发行为最常用的程序是“消退-复燃模型”。该概念最初由 Pavlov 和 Skinner 提出，强化操作性反应的概念直到 1971 年才被应用于成瘾研究（Stretch 等人，Can J Physiol Pharmacol 49:581-589, 1971），并且直到 10 年后才发表了现在全球范围内使用的复燃动物模型的第一个报告（De Wit 和 Stewart，Psychopharmacology 75:134-143, 1981）。根据该模型，阿片类药物通常像人类一样静脉内自我给药，尽管这些研究中最常使用啮齿动物，但也可以使用包括非人类灵长类动物、狗、猫和鸽子在内的多种物种。根据所研究的物种，有几种操作性反应可供选择。例如，对于啮齿动物，通常使用杠杆按压或鼻戳反应，而对于非人类灵长类动物，通常使用面板按压反应。在本章中，我们描述了一种简单且易于重现的大鼠海洛因觅药复燃方案，该方案已被证明可用于研究海洛因复发的神经生物学机制和增强海洛因觅药行为恢复的易感性因素。
