Noribogaine reduces nicotine self-administration in rats

• Published in: Journal of psychopharmacology (Oxford) Vol. 29; no. 6; pp. 704 - 711
• Main Authors: Chang, Qing, Hanania, Taleen, Mash, Deborah C, Maillet, Emeline L
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.06.2015
• Subjects: Animals; Dose-Response Relationship, Drug; Ibogaine - analogs & derivatives; Ibogaine - pharmacology; Male; Nicotine - administration & dosage; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - metabolism; Self Administration - methods; Smoking Cessation - methods; Tobacco Use Disorder - drug therapy; Tobacco Use Disorder - metabolism; Varenicline - pharmacology; α7 nicotinic acetylcholine receptor antagonist; Food self-administration; α3β4 nicotinic acetylcholine receptor antagonist; addiction
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881115584461

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.