Hutsell Blake A, Banks Matthew L
Department of Pharmacology and Toxicology, Virginia Commonwealth University.
Exp Clin Psychopharmacol. 2017 Dec;25(6):441-447. doi: 10.1037/pha0000154.
Emerging human laboratory and preclinical drug self-administration data suggest that a history of contingent abused drug exposure impairs performance in operant discrimination procedures, such as delayed nonmatching-to-sample (DNMTS), that are hypothesized to assess components of executive function. However, these preclinical discrimination studies have exclusively used food as the reinforcer and the effects of drugs as reinforcers in these operant procedures are unknown. The present study determined effects of contingent intravenous remifentanil injections on DNMTS performance hypothesized to assess 1 aspect of executive function, working memory. Daily behavioral sessions consisted of 2 components with sequential intravenous remifentanil (0, 0.01-1.0 μg/kg/injection) or food (0, 1-10 pellets) availability in nonopioid dependent male rhesus monkeys (n = 3). Remifentanil functioned as a reinforcer in the DNMTS procedure. Similar delay-dependent DNMTS accuracy was observed under both remifentanil- and food-maintained components, such that higher accuracies were maintained at shorter (0.1-1.0 s) delays and lower accuracies approaching chance performance were maintained at longer (10-32 s) delays. Remifentanil maintained significantly lower initial DNMTS accuracy compared to food. Reinforcer magnitude was not an important determinant of DNMTS accuracy for either remifentanil or food. These results extend the range of experimental procedures under which drugs function as reinforcers. Furthermore, the selective remifentanil-induced decrease in initial DNMTS accuracy is consistent with a selective impairment of attentional, but not memorial, processes. (PsycINFO Database Record
新出现的人体实验室和临床前药物自我给药数据表明，偶然接触滥用药物的经历会损害操作性辨别程序中的表现，如延迟非匹配样本（DNMTS），该程序被假设用于评估执行功能的组成部分。然而，这些临床前辨别研究仅使用食物作为强化物，而药物作为这些操作性程序中的强化物的效果尚不清楚。本研究确定了偶然静脉注射瑞芬太尼对DNMTS表现的影响，该表现被假设用于评估执行功能的一个方面，即工作记忆。每日行为实验包括两个部分，在非阿片类药物依赖的雄性恒河猴（n = 3）中依次提供静脉注射瑞芬太尼（0，0.01 - 1.0 μg/kg/注射）或食物（0，1 - 10粒）。瑞芬太尼在DNMTS程序中起到了强化物的作用。在瑞芬太尼和食物维持的部分中观察到了类似的延迟依赖性DNMTS准确性，即在较短（0.1 - 1.0秒）延迟时保持较高的准确性，而在较长（10 - 32秒）延迟时保持较低的准确性，接近随机表现。与食物相比，瑞芬太尼维持的初始DNMTS准确性显著较低。强化物的大小对于瑞芬太尼或食物来说都不是DNMTS准确性的重要决定因素。这些结果扩展了药物作为强化物起作用的实验程序范围。此外，瑞芬太尼选择性地导致初始DNMTS准确性下降，这与注意力而非记忆过程的选择性损害一致。（PsycINFO数据库记录）
