Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats.

Alcohol-preferring (P), Fawn-Hooded (FH) and alcohol-accepting (AA) rats were injected intraperitoneally (IP) or subcutaneously (SC) with different doses (10, 30, and 60 mg/kg) of Ibogaine or vehicle. In a separate experiment, FH rats were administered intragastrically (IG) with either 60 mg/kg of Ibogaine or vehicle for 5 days. In addition, the effects of Ibogaine on blood alcohol concentrations were measured. Our data show that, contrary to the SC administration of Ibogaine, IP administration of the agent significantly and dose-dependently reduced alcohol intake in these rats. Subchronic IG administration of 60 mg/kg of Ibogaine into FH rats significantly reduced alcohol intake without the development of tolerance or a significant effect on food or water intake. A single IP injection of 60 mg/kg Ibogaine into FH rats did not affect the blood alcohol levels. These results show that Ibogaine when injected IP or IG, but not SC, can significantly reduce alcohol intake without an effect on blood alcohol concentrations or food intake. These findings may suggest the involvement of Ibogaine's metabolite(s) in reducing alcohol intake. Although the neuronal mechanism(s) of action of Ibogaine on the regulation of alcohol intake is not fully understood, it is speculated that Ibogaine or its metabolite(s) exerts its attenuating effect on alcohol intake by modulating neurotransmitters/neuromodulators proposed to be involved in regulation of alcohol consumption.