Anatabine significantly decreases nicotine self-administration.

Abstract

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.