Intramural Research Program, NIDA, NIH, Baltimore, USA.
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Neuropsychopharmacology. 2021 Dec;46(13):2350-2357. doi: 10.1038/s41386-021-01148-6. Epub 2021 Aug 16.
Social reinforcement-based treatments are effective for many, but not all, people with addictions to drugs. We recently developed an operant rat model that mimics features of one such treatment, the community-reinforcement approach. In this model, rats uniformly choose social interaction over methamphetamine or heroin. Abstinence induced by social preference protects against the incubation of drug-seeking that would emerge during forced abstinence. Here, we determined whether these findings generalize to cocaine and whether delaying or increasing effort for social interaction could reveal possibly human-relevant individual differences in responsiveness. We trained male and female rats for social self-administration (6 days) and then for cocaine self-administration, initially for 2-h/day for 4 days, and then for 12-h/day continuously or intermittently for 8 days. We assessed relapse to cocaine seeking after 1 and 15 days. Between tests, the rats underwent either forced abstinence or social-choice-induced abstinence. After establishing stable social preference, we manipulated the delay for both rewards or for social reward alone, or the response requirements (effort) for social reward. Independent of cocaine-access conditions and sex, operant social interaction inhibited cocaine self-administration and prevented incubation of cocaine seeking. Preference for social access was decreased by the delay of both rewards or social reward alone, or by increased response requirements for social reward, with notable individual variability. This choice procedure can identify mechanisms of individual differences in an animal model of cocaine use and could thereby help screen medications for people who are relatively unresponsive to treatments based on rewarding social interaction.
基于社会强化的治疗方法对许多,但不是所有,药物成瘾者有效。我们最近开发了一种操作式大鼠模型,模拟了一种这样的治疗方法,即社区强化方法。在这种模型中,大鼠均匀地选择社交互动而不是甲基苯丙胺或海洛因。社交偏好引起的禁欲可以防止在强制禁欲期间出现的觅药潜伏期。在这里,我们确定了这些发现是否适用于可卡因,以及延迟或增加社交互动的努力是否可以揭示可能与人类相关的反应性个体差异。我们训练雄性和雌性大鼠进行社交自我给药(6 天),然后进行可卡因自我给药,最初连续 4 天每天 2 小时,然后连续 8 天每天 12 小时或间歇性给药。我们评估了 1 天和 15 天后可卡因寻求的复发情况。在测试之间,大鼠经历了强制禁欲或社交选择引起的禁欲。在建立稳定的社交偏好后,我们操纵了两种奖励的延迟或仅社交奖励的延迟,或者操纵了社交奖励的反应要求(努力)。独立于可卡因获取条件和性别,操作性社交互动抑制可卡因自我给药并防止可卡因寻求的潜伏期。社交访问的偏好因两种奖励或仅社交奖励的延迟或社交奖励的反应要求增加而降低,个体差异显著。这种选择程序可以在可卡因使用的动物模型中确定个体差异的机制,从而有助于为对基于奖励社交互动的治疗反应相对不敏感的人筛选药物。