title: 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.
authors.affiliation: Behavioral Pharmacology, PsychoGenics Inc., Tarrytown, NY, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Behavioral Pharmacology, PsychoGenics Inc., Tarrytown, NY, USA.
authors.forename: Taleen
authors.initials: T
authors.lastname: Hanania
authors.affiliation: R&D Laboratory, DemeRx, Inc., Miami, FL, USA Miller School of Medicine, Miami, FL, USA.
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
authors.affiliation: R&D Laboratory, DemeRx, Inc., Miami, FL, USA emaillet@demerx.us.
authors.forename: Emeline L
authors.initials: EL
authors.lastname: Maillet
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D012646:Self Administration / Q000379:methods; D016540:Smoking Cessation / Q000379:methods; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000378:metabolism; D000068580:Varenicline / Q000494:pharmacology
chemical_list: D011978:Receptors, Nicotinic; D007050:Ibogaine; D009538:Nicotine; C094385:noribogaine; D000068580:Varenicline
keywords: Food self-administration; addiction; α3β4 nicotinic acetylcholine receptor antagonist; α7 nicotinic acetylcholine receptor antagonist