18-Methoxycoronardine attenuates nicotine-induced dopamine release and nicotine preferences in rats

Two studies were conducted to assess, in vivo, potential anti-nicotinic effects of the iboga alkaloid ibogaine and its synthetic congener 18-methoxycoronaridine (18-MC). As previously demonstrated for ibogaine, using microdialysis, pretreatment (19h beforehand) with 18-MC (40 mg/kg, i.p.) significantly attenuated nicotine-induced dopamine release in the nucleus accumbens of awake and freely moving rats. In an oral model of nicotine self-administration, both ibogaine and 18-MC decreased rats' preferences for nicotine for at least 24 h. Acutely, during the first hour after administration, ibogaine depressed responding for water as well as for nicotine; however, during this same time, 18-MC reduced nicotine intake without affecting responding for water. The results suggest that 18-MC might be the prototype of a new treatment for smoking.