Department of Psychology, BBSRB, University of Kentucky, Room 448C, Lexington, KY, 40536-0509, USA.
Psychopharmacology (Berl). 2017 Dec;234(23-24):3499-3506. doi: 10.1007/s00213-017-4734-2. Epub 2017 Sep 15.
Opioid abuse is a major problem around the world. Identifying environmental factors that contribute to opioid abuse and addiction is necessary for decreasing this epidemic. In rodents, environmental enrichment protects against the development of low dose stimulant self-administration, but studies examining the effect of enrichment and isolation (compared to standard housing) on the development of intravenous opioid self-administration have not been conducted. The present study investigated the role of environmental enrichment on self-administration of the short-acting μ-opioid remifentanil.
Rats were raised in an enriched condition (Enr), standard condition (Std), or isolated condition (Iso) beginning at 21 days of age and were trained to lever press for 1 or 3 μg/kg/infusion remifentanil in young adulthood. Acquisition of self-administration and responding during increasing fixed ratio requirements were assessed, and a dose-response curve was generated.
In all phases, Enr rats lever pressed significantly less than Std and Iso rats, with Enr rats pressing between 9 and 40% the amount of Iso rats. Enr rats did not acquire remifentanil self-administration when trained with 1 μg/kg/infusion, did not increase responding over increasing FR when trained at either dose, and their dose-response curves were flattened compared to Std and Iso rats. When expressed as economic demand curves, Enr rats displayed a decrease in both essential value (higher α) and reinforcer intensity (Q ) compared to Std and Iso rats at the 1 μg/kg/infusion training dose.
Environmental enrichment reduced remifentanil intake, suggesting that social and environmental novelty may protect against opioid abuse.
阿片类药物滥用是一个全球性的主要问题。确定导致阿片类药物滥用和成瘾的环境因素对于减少这一流行至关重要。在啮齿动物中,环境丰富可以预防低剂量兴奋剂的自我给药,但尚未研究环境丰富和隔离(与标准住房相比)对静脉内阿片类药物自我给药发展的影响。本研究调查了环境丰富对短效μ-阿片类药物瑞芬太尼自我给药的作用。
从 21 天大开始,大鼠在丰富条件(Enr)、标准条件(Std)或隔离条件(Iso)下饲养,并在成年早期接受 1 或 3μg/kg/ 输注瑞芬太尼的按压训练。评估了自我给药的获得和递增固定比率要求期间的反应,并生成了剂量-反应曲线。
在所有阶段,Enr 大鼠的按压次数明显少于 Std 和 Iso 大鼠,Enr 大鼠的按压次数为 Iso 大鼠的 9%至 40%。当用 1μg/kg/ 输注训练时,Enr 大鼠未获得瑞芬太尼自我给药,在任何剂量下都未增加反应,并且其剂量-反应曲线比 Std 和 Iso 大鼠平坦。当用经济需求曲线表示时,与 Std 和 Iso 大鼠相比,在 1μg/kg/ 输注训练剂量下,Enr 大鼠的基本价值(较高的α)和强化值(Q)都降低了。
环境丰富减少了瑞芬太尼的摄入,这表明社会和环境新奇可能有助于预防阿片类药物滥用。