Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in rats

The ibogaine derivative 18-methoxycoronaridine (18-MC) has been found to decrease self-administration of morphine, nicotine and alcohol in rats after systemic injection. However oral dosing is the preferred route clinically. The current study evaluated the effect of oral 18-MC dosing in rats on alcohol and nicotine self-administration. For the nicotine study, young adult female Sprague-Dawley rats were fitted with IV jugular infusion catheters and trained for nicotine self-administration in 45 min. sessions. At weekly intervals they were administered by oral gavage doses of 18-MC (0, 10, 20 and 40 mg/kg) following a repeated measures counterbalanced design twice. Acute oral 18-MC, at the 40 mg/kg dosage, significantly reduced nicotine self-administration. There was a differential effect of 18-MC with rats above or below the median level of nicotine self-administration during the pretreatment baseline performance. Rats with lower baseline performance showed a significant reduction in nicotine self-administration with the 40 mg/kg dosage, while those in the higher baseline group did not show a significant effect of 18-MC. In alcohol studies, the effects of the same doses of 18-MC were tested in both male and female alcohol preferring (P) rats that had free access to water and alcohol (10% v/v) 6 h/day. The results show that 18-MC dose-dependently reduced alcohol intake in both male and female rats. All doses caused significant reductions in alcohol self-administration. These data reinforce previous findings that 18-MC is significantly effective in reducing alcohol intake and nicotine self-administration. The finding that 18-MC is also effective orally makes it advantageous for further development as a possible new therapy for treating alcoholism as well as smoking addiction.