Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, United States.
Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, United States.
Drug Alcohol Depend. 2021 Jun 1;223:108707. doi: 10.1016/j.drugalcdep.2021.108707. Epub 2021 Apr 10.
Although most individuals with cocaine use disorder also abuse alcohol, little is known about the behavioral and pharmacological mechanisms that promote co-abuse. For example, it is unclear whether prior experience with alcohol renders individuals more sensitive to cocaine when it is subsequently experienced.
This study examined the effects of chronic ethanol consumption on subsequent cocaine reinforcement in rhesus monkeys. Six monkeys consumed 2.0 g/kg ethanol in a binge-drinking paradigm and 6 monkeys drank a non-alcoholic solution 5 days per week. After 9 months, each monkey's sensitivity to acquiring cocaine self-administration was determined. Monkeys performed an operant response resulting in food pellet delivery under a fixed-ratio 30 schedule of reinforcement. Saline, then ascending doses of cocaine, were substituted for food pellets until a cocaine dose was reached at which the number of cocaine injections delivered differed significantly from saline injections delivered. Following acquisition, a complete cocaine dose-effect curve was generated to determine whether ethanol consumption altered the reinforcing potency of cocaine determined by calculating the ED of the ascending limb of each subject's curve.
Although individual variability was observed, the cocaine dose which initially served as a reinforcer did not differ between ethanol-drinking and control groups and, within the ethanol-drinking group, was not related to the amount of ethanol consumed. Moreover, the reinforcing potency of cocaine did not differ between groups.
Taken together, the data suggest that a history of binge-like alcohol consumption does not affect sensitivity to cocaine when it is subsequently first experienced.
尽管大多数可卡因使用障碍患者也滥用酒精,但对于促进共滥用的行为和药理学机制知之甚少。例如,目前尚不清楚个体在随后接触可卡因时,先前接触酒精是否会使他们对可卡因更敏感。
本研究检查了慢性乙醇消耗对恒河猴随后可卡因强化的影响。六只猴子以 binge-drinking 范式摄入 2.0 g/kg 乙醇,六只猴子每周五天饮用非酒精溶液。9 个月后,确定每只猴子对可卡因自我给药的敏感性。猴子执行一个操作性反应,导致在固定比率 30 的强化计划下输送食物丸。用生理盐水替代食物丸,然后是递增剂量的可卡因,直到达到一个可卡因剂量,与生理盐水剂量相比,可卡因剂量显著不同。在获得可卡因剂量效应曲线后,计算每个研究对象曲线上升支的 ED,以确定乙醇消耗是否改变可卡因的强化效力,从而确定可卡因的强化效力。
尽管观察到个体差异,但乙醇组和对照组的起始可卡因剂量没有差异,并且在乙醇组中,该剂量与消耗的乙醇量无关。此外,两组之间的可卡因强化效力没有差异。
综上所述,数据表明, binge-like 酒精消耗史并不会影响个体在首次接触可卡因时的敏感性。