TY - JOUR
T1 - Noribogaine reduces nicotine self-administration in rats
AU - Chang, Qing
AU - Hanania, Taleen
AU - Mash, Deborah C.
AU - Maillet, Emeline L.
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was financially supported by DemeRx, Inc.
Publisher Copyright:
© The Author(s) 2015.
PY - 2015/6/6
Y1 - 2015/6/6
N2 - 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.
AB - 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.
KW - Food self-administration
KW - addiction
KW - α3β4 nicotinic acetylcholine receptor antagonist
KW - α7 nicotinic acetylcholine receptor antagonist
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U2 - 10.1177/0269881115584461
DO - 10.1177/0269881115584461
M3 - Article
C2 - 25995321
AN - SCOPUS:84930671705
VL - 29
SP - 704
EP - 711
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
SN - 0269-8811
IS - 6
ER -