University of Michigan, USA.
J Exp Anal Behav. 2011 Jan;95(1):75-89. doi: 10.1901/jeab.2011.95-75.
Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been applied to this question. The present study assessed whether mild morphine withdrawal would increase demand for or choice of remifentanil or cocaine. Four rhesus monkeys chose between remifentanil and cocaine during daily sessions. Demand curves for both drugs were subsequently obtained. The effects of daily injections of 3.2 mg/kg morphine on both choice and demand for these drugs was assayed 3 and 20.5 hr after each morphine injection, and then during a postmorphine period. Three hours following morphine injections, choice of remifentanil over cocaine decreased and demand for remifentanil--but not cocaine--became more elastic. During morphine withdrawal (20.5 hr postinjection), choice of remifentanil increased and remifentanil demand became more inelastic in 3 of 4 monkeys. Cocaine demand also became more inelastic during this period. Four to five weeks following the morphine regimen, demand for both drugs was more inelastic relative to the initial determination. The results suggest that both the relative and absolute reinforcing effectiveness of remifentanil decreased following morphine administration and increased during morphine withdrawal. The absolute reinforcing effectiveness of cocaine also increased during morphine withdrawal. In addition, extended exposure to drug self-administration and/or exposure to the morphine regimen produced long-term increases in demand for both drugs.
选择程序表明,阿片类药物戒断期间,阿片类药物的相对强化效力增加。需求曲线,即强化值的绝对衡量标准,尚未应用于这个问题。本研究评估了轻度吗啡戒断是否会增加对瑞芬太尼或可卡因的需求或选择。四只恒河猴在每日的实验中选择瑞芬太尼和可卡因。随后获得了这两种药物的需求曲线。每天注射 3.2 毫克/千克吗啡对这两种药物的选择和需求的影响,在每次吗啡注射后 3 小时和 20.5 小时进行检测,然后在吗啡后期间进行检测。在吗啡注射后 3 小时,瑞芬太尼对可卡因的选择减少,而瑞芬太尼的需求变得更加有弹性,而可卡因的需求则没有变化。在吗啡戒断期间(注射后 20.5 小时),3 只猴子中的 4 只增加了对瑞芬太尼的选择,而瑞芬太尼的需求变得更加缺乏弹性。在此期间,可卡因的需求也变得更加缺乏弹性。在吗啡方案结束后的 4 到 5 周,相对于最初的测定,两种药物的需求都变得更加缺乏弹性。研究结果表明,瑞芬太尼在吗啡给药后其相对和绝对强化效力降低,而在吗啡戒断期间则增加。可卡因的绝对强化效力在吗啡戒断期间也增加。此外,长期接触药物自我给药和/或接触吗啡方案会导致对这两种药物的需求长期增加。