Mello Nancy K, Fivel Peter A, Kohut Stephen J, Caine S Barak
McLean Hospital/Harvard Medical School.
Exp Clin Psychopharmacol. 2014 Feb;22(1):1-8. doi: 10.1037/a0035409.
Nicotine addiction is associated with many lethal disorders (cancer, cardiovascular and pulmonary disease), and more effective medications to aid smoking cessation are urgently needed. Anatabine is 1 of the most abundant minor tobacco alkaloids, but relatively little is known about its interactions with the abuse-related effects of nicotine. The acute effects of anatabine or saline on nicotine- and food-maintained responding were examined in 7 rhesus monkeys (Macaca mulatta). Nicotine (0.01 mg/kg/inj, base) and banana-flavored food pellets (1 g) were available under a second-order schedule (FR 2 [VR 16:S]). Anatabine or saline injections were administered 15 min before the 11:00 a.m. food self-administration session began. Anatabine (0.18-3.2 mg/kg, IM) dose-dependently reduced nicotine self-administration (0.01 mg/kg/inj) (p = .036-0.0003). Food-maintained responding was decreased only at the highest dose of anatabine (3.2 mg/kg; p = .003). Each monkey returned to baseline levels of nicotine self-administration after anatabine treatment, and there was no evidence of catheter malfunction. Next, the effects of anatabine and saline on the nicotine dose-effect curve (0.001-0.1 mg/kg/inj) were evaluated. Anatabine (0.32 and 1.0 mg/kg, IM) decreased the peak of the nicotine dose-effect curve (p < .001 - p < .0001), with no significant effect on food-maintained responding. The abuse liability of anatabine also was examined, and monkeys did not self-administer anatabine (0.0032-0.32 mg/kg/inj) above saline levels. These findings are consistent with anatabine's effects on nicotine self-administration in rats (Caine et al., 2014). These data suggest that anatabine could be an effective agonist medication for treatment of nicotine addiction.
尼古丁成瘾与许多致命疾病（癌症、心血管疾病和肺部疾病）相关，因此迫切需要更有效的药物来辅助戒烟。新烟草碱是含量最丰富的微量烟草生物碱之一，但人们对其与尼古丁成瘾相关效应的相互作用了解相对较少。在7只恒河猴（猕猴）身上研究了新烟草碱或生理盐水对尼古丁维持和食物维持反应的急性影响。尼古丁（0.01毫克/千克/注射，碱）和香蕉味食物颗粒（1克）按照二阶程序（FR 2 [VR 16:S]）提供。在上午11:00的食物自我给药环节开始前15分钟注射新烟草碱或生理盐水。新烟草碱（0.18 - 3.2毫克/千克，肌肉注射）剂量依赖性地减少了尼古丁自我给药（0.01毫克/千克/注射）（p = 0.036 - 0.0003）。仅在新烟草碱最高剂量（3.2毫克/千克）时食物维持反应降低（p = 0.003）。新烟草碱治疗后，每只猴子的尼古丁自我给药水平都恢复到了基线，且没有导管故障的迹象。接下来，评估了新烟草碱和生理盐水对尼古丁剂量效应曲线（0.001 - 0.1毫克/千克/注射）的影响。新烟草碱（0.32和1.0毫克/千克，肌肉注射）降低了尼古丁剂量效应曲线的峰值（p < 0.001 - p < 0.0001），对食物维持反应无显著影响。还研究了新烟草碱的成瘾可能性，猴子不会自我给药高于生理盐水水平的新烟草碱（0.0032 - 0.32毫克/千克/注射）。这些发现与新烟草碱对大鼠尼古丁自我给药的影响一致（凯恩等人，2014年）。这些数据表明，新烟草碱可能是治疗尼古丁成瘾的有效激动剂药物。
