Noribogaine reduces nicotine self-administration in rats

Abstract

Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats' levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation.

Keywords: Food self-administration; addiction; α3β4 nicotinic acetylcholine receptor antagonist; α7 nicotinic acetylcholine receptor antagonist.

Figure 1.

Molecular structure of noribogaine. (15S,17R)-17-ethyl-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4(9),5,7-tetraen-7-ol (CAS no. 481-88-9).

Figure 2.

Effects of noribogaine and varenicline on nicotine self-administration in rats. Data represent mean±standard error of the mean (SEM) of n=13 animals. #p<0.10; ***p<0.001 compared to vehicle or saline treatment. The y-axis shows the total number of animal-initiated nicotine infusions during the one-hour test session.

Figure 3.

Effects of noribogaine and varenicline in food maintained responding rats. Data represent mean±standard error of the mean (SEM) of n=8 animals. *p<0.05; ***p<0.001 compared to vehicle or saline treatment. The y-axis shows the total number of food pellets obtained by the animals during the one-hour test session.