Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
Nat Protoc. 2020 Apr;15(4):1542-1559. doi: 10.1038/s41596-020-0296-6. Epub 2020 Mar 20.
It is difficult to translate results from animal research on addiction to an understanding of the behavior of human drug users. Despite decades of basic research on neurobiological mechanisms of drug addiction, treatment options remain largely unchanged. A potential reason for this is that mechanistic studies using rodent models do not incorporate a critical facet of human addiction: volitional choices between drug use and non-drug social rewards (e.g., employment and family). Recently, we developed an operant model in which rats press a lever for rewarding social interaction with a peer and then choose between an addictive drug (heroin or methamphetamine) and social interaction. Using this model, we showed that rewarding social interaction suppresses drug self-administration, relapse to drug seeking, and brain responses to drug-associated cues. Here, we describe a protocol for operant social interaction using a discrete-trial choice between drugs and social interaction that causes voluntary abstinence from the drug and tests for incubation of drug craving (the time-dependent increase in drug seeking during abstinence). This protocol is flexible but generally requires 8-9 weeks for completion. We also provide a detailed description of the technical requirements and procedures for building the social self-administration and choice apparatus. Our protocol provides a reliable way to study the role of operant social reward in addiction and addiction vulnerability in the context of choices. We propose that this protocol can be used to study brain mechanisms of operant social reward and potentially impairments in social reward in animal models of psychiatric disorders and pain.
将动物成瘾研究的结果转化为对人类吸毒者行为的理解是困难的。尽管对药物成瘾的神经生物学机制进行了几十年的基础研究，但治疗选择仍然基本没有改变。造成这种情况的一个潜在原因是，使用啮齿动物模型进行的机制研究没有纳入人类成瘾的一个关键方面：在药物使用和非药物社会奖励（例如就业和家庭）之间进行自主选择。最近，我们开发了一种操作性模型，在此模型中，大鼠按压杠杆以获得与同伴进行奖励性社交互动的机会，然后在成瘾药物（海洛因或甲基苯丙胺）和社交互动之间做出选择。使用该模型，我们发现奖励性社交互动会抑制药物自我给药、药物寻求复发和与药物相关线索的大脑反应。在这里，我们描述了一种使用药物和社交互动之间的离散试验选择来进行操作性社交互动的方案，该方案可导致自愿戒除药物，并测试药物渴望的潜伏期（在戒断期间药物寻求的时间依赖性增加）。该方案具有灵活性，但通常需要 8-9 周才能完成。我们还提供了详细描述，介绍了构建社交自我管理和选择仪器的技术要求和程序。我们的方案提供了一种可靠的方法来研究操作性社交奖励在成瘾和成瘾易感性中的作用，以及在选择背景下的作用。我们提出，该方案可用于研究精神疾病和疼痛动物模型中操作性社交奖励的大脑机制，以及社交奖励可能受损的情况。
