Minhas Meenu, Leri Francesco
Department of Psychology, University of Guelph, Ontario, Canada, N1G 2W1.
Department of Psychology, University of Guelph, Ontario, Canada, N1G 2W1.
Drug Alcohol Depend. 2014 May 1;138:24-31. doi: 10.1016/j.drugalcdep.2014.01.007. Epub 2014 Feb 7.
It has been proposed that relapse vulnerability in previously dependent individuals results from augmentation of drug-induced reinforcement due to repeated associations between the interoceptive properties of the drug and reduction of acute withdrawal distress.
To test this hypothesis, male Sprague-Dawley rats self-administered 0.05 mg/kg/inf heroin on continuous reinforcement (CR) and progressive ratio (PR) schedules. During this period, they also received injections of vehicle or escalating doses of heroin. Following tests of naloxone-precipitated withdrawal, as well as a drug-free period (4 days), and extinction (9 sessions), they were pre-treated with vehicle or yohimbine (0.5mg/kg, IV) and tested for resumption of heroin self-administration (0.05 mg/kg/inf) on CR and PR schedules, or tested for reinstatement in extinction conditions.
Increased self-administration on the CR schedule was observed in the heroin-injected rats, but no group differences were observed on the PR schedule, in spite of greater signs of withdrawal precipitated by naloxone in the heroin-injected rats. More importantly, there were no group differences in resumption of heroin self-administration, and this was not altered by yohimbine.
These results suggest that relapse vulnerability cannot be uniquely ascribed to enhanced reinforcing action of drugs; contextual and other conditioning factors must play a role in modulating resumption of drug intake after abstinence.
有人提出，既往有药物依赖史的个体复发易感性是由于药物的内感受特性与急性戒断痛苦减轻之间反复关联，导致药物诱导的强化作用增强所致。
为验证这一假设，雄性Sprague-Dawley大鼠在连续强化（CR）和累进比率（PR）方案下自行注射0.05mg/kg/次海洛因。在此期间，它们还接受了注射赋形剂或递增剂量海洛因的处理。在进行纳洛酮诱发戒断测试、药物戒断期（4天）以及消退期（9次）后，它们先接受赋形剂或育亨宾（0.5mg/kg，静脉注射）预处理，然后在CR和PR方案下测试海洛因自行注射（0.05mg/kg/次）的恢复情况，或在消退条件下测试复吸情况。
注射海洛因的大鼠在CR方案下自行注射量增加，但在PR方案下未观察到组间差异，尽管注射海洛因的大鼠中纳洛酮诱发的戒断症状更明显。更重要的是，海洛因自行注射的恢复情况在组间没有差异，且这不受育亨宾的影响。
这些结果表明，复发易感性不能单纯归因于药物强化作用增强；情境及其他条件因素在调节戒断后药物摄入恢复方面必定发挥作用。
