Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Neuroscience Research Building, 320 W. 15th Street, Suite 300B, Indianapolis, IN, 46202-2266, USA.
Psychopharmacology (Berl). 2019 Jun;236(6):1887-1900. doi: 10.1007/s00213-019-5174-y. Epub 2019 Feb 13.
Simultaneous alcohol and nicotine consumption occurs in the majority of individuals with alcohol use disorder (AUD) and nicotine dependence. Varenicline (Var) is used to assist in the cessation of nicotine use, while naltrexone (Nal) is the standard treatment for AUD. Despite evidence that ethanol (EtOH) and nicotine (NIC) co-use produces unique neuroadaptations, preclinical research has focused on the effects of pharmacotherapeutics on a single reinforcer. The current experiments examined the effects of Var and Nal on EtOH, NIC, or EtOH+NIC intake.
Animals were randomly assigned to one of four drinking conditions of 24-h access to a three-bottle choice paradigm, one of which always contained water. Drinking conditions were water only, 0.07 and 0.14 mg/mL NIC (NIC only), 15% and 30% EtOH (EtOH only), or 15% and 30% EtOH with 0.14 mg/mL NIC (EtOH+NIC). The effects of Var (0, 1, or 2 mg/kg) or Nal (0, 1, or 10 mg/kg) injections on maintenance and relapse consumption were determined during four consecutive days.
Var reduced maintenance and relapse NIC intake but had no effect on EtOH or EtOH+NIC drinking. Conversely, Nal reduced EtOH maintenance and relapse drinking, but had no effect on NIC or EtOH+NIC drinking.
The results indicate the standard pharmacological treatments for nicotine dependence and AUD were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC co-use/abuse. These findings suggest that co-abuse may promote unique neuroadaptations that require models of polysubstance abuse to develop pharmacotherapeutics to treat AUD and nicotine dependence.
在大多数患有酒精使用障碍（AUD）和尼古丁依赖的个体中，同时摄入酒精和尼古丁的情况较为常见。瓦伦尼克林（Var）用于辅助戒烟，而纳曲酮（Nal）是 AUD 的标准治疗方法。尽管有证据表明乙醇（EtOH）和尼古丁（NIC）共同使用会产生独特的神经适应性，但临床前研究主要集中在药物治疗对单一强化物的影响上。本实验研究了 Var 和 Nal 对 EtOH、NIC 或 EtOH+NIC 摄入的影响。
动物被随机分配到四种 24 小时自由饮用三瓶选择范式的饮酒条件之一，其中一种始终含有水。饮酒条件分别为：仅饮水、0.07 和 0.14mg/mL 的 NIC（仅 NIC）、15%和 30%的 EtOH（仅 EtOH）或 15%和 30%的 EtOH 与 0.14mg/mL 的 NIC（EtOH+NIC）。在连续四天内，通过注射 Var（0、1 或 2mg/kg）或 Nal（0、1 或 10mg/kg）来确定药物对维持和复发消费的影响。
Var 降低了维持和复发的 NIC 摄入量，但对 EtOH 或 EtOH+NIC 饮酒没有影响。相反，Nal 降低了 EtOH 的维持和复发饮酒量，但对 NIC 或 EtOH+NIC 饮酒没有影响。
研究结果表明，用于尼古丁依赖和 AUD 的标准药物治疗方法可有效降低目标强化物的消耗，但均不能减少 EtOH+NIC 的共同使用/滥用。这些发现表明，共同滥用可能促进了独特的神经适应性，需要开发多药物滥用模型来开发治疗 AUD 和尼古丁依赖的药物治疗方法。
