Department of Physiology and Pharmacology, Graduate Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Department of Physiology and Pharmacology, Graduate Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Drug Alcohol Depend. 2023 Oct 1;251:110952. doi: 10.1016/j.drugalcdep.2023.110952. Epub 2023 Sep 2.
Individuals who use cocaine have high rates of co-morbid alcohol use and when ethanol and cocaine are administered concurrently, the metabolite cocaethylene is formed. Cocaethylene is equipotent to cocaine in blocking dopamine reuptake and substitutes for cocaine in drug discrimination studies. However, no previous work has directly compared the reinforcing strength of cocaine to cocaethylene.
In Experiment 1, three individually-housed adult male rhesus macaques self-administer cocaine under a progressive-ratio (PR) schedule of reinforcement, during daily 4-hr sessions. Under this schedule, the primary dependent variable is the number of injections received, or the break point (BP). Saline, cocaine (0.001-0.3mg/kg/injection) and cocaethylene (0.0003-0.1mg/kg/injection) dose-response curves were determined. In Experiment 2, two female cynomolgus and one rhesus macaque responded under a concurrent schedule of drug (cocaine or cocaethylene) vs. 1.0-g banana-flavored food pellets, during daily 1-hr sessions.
Both cocaine and cocaethylene functioned as reinforcers under the PR and concurrent choice schedules of reinforcement. Under the PR schedule, peak BPs were not significantly different, nor were ED50 values on the ascending limb, suggesting that cocaethylene has equal reinforcing strength and potency to cocaine. Under the concurrent drug-food choice procedure, cocaethylene was also equally potent to cocaine.
Under two schedules of reinforcement designed to assess reinforcing strength, cocaethylene and cocaine were equipotent and of equal reinforcing strength. Because cocaethylene has a longer duration of action, it is important for studies designed to evaluate treatments for cocaine use to also consider the effects of these interventions on cocaethylene.
使用可卡因的个体有很高的共病性酒精使用率，当乙醇和可卡因同时给药时，会形成代谢物可乐因。可乐因在阻断多巴胺再摄取方面与可卡因等效，并在药物辨别研究中替代可卡因。然而，以前没有研究直接比较可卡因和可乐因的强化强度。
在实验 1 中，三只单独饲养的成年雄性恒河猴在递增比率（PR）强化方案下自我给予可卡因，每天 4 小时的时段。在这种方案下，主要的因变量是注射次数，即断点（BP）。确定了盐水、可卡因（0.001-0.3mg/kg/注射）和可乐因（0.0003-0.1mg/kg/注射）的剂量反应曲线。在实验 2 中，两只食蟹猴和一只恒河猴在药物（可卡因或可乐因）与 1.0 克香蕉味食物丸的同时出现的时间表下做出反应，每天 1 小时的时段。
可卡因和可乐因在 PR 和同时出现的强化时间表下都具有强化作用。在 PR 时间表下，峰值 BP 没有显著差异，上升支的 ED50 值也没有差异，表明可乐因具有与可卡因相等的强化强度和效力。在同时出现的药物-食物选择程序下，可乐因对可卡因的效力也相等。
在两种强化时间表下，评估强化强度，可乐因和可卡因具有同等效力，并且具有同等的强化强度。由于可乐因的作用时间较长，因此对于评估可卡因使用治疗的研究来说，考虑这些干预措施对可乐因的影响很重要。
