Noribogaine reduces nicotine self-administration in rats.

Summary

Imagine a new treatment that could cut nicotine intake by nearly two-thirds. A compound called noribogaine, known for its action as an α3β4 nicotinic acetylcholine receptor antagonist and α7 nicotinic acetylcholine receptor antagonist, was explored for its potential in combating nicotine addiction. In controlled settings, it significantly reduced nicotine self-administration by up to 64%, proving as effective as a leading smoking cessation drug. Crucially, it had a much smaller effect on food self-administration, suggesting a targeted impact on drug-seeking behavior. These positive findings offer significant hope for developing a new therapy to help people overcome nicotine dependence.

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.

Tags