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

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2016-11, Vol.150-151, p.153-157
• Main Authors: Rezvani, Amir H, Cauley, Marty C, Slade, Susan, Wells, Corinne, Glick, Stanley, Rose, Jed E, Levin, Edward D
• Format: Article
• Language: English
• Subjects: Administration, Oral; Alcohol Drinking - drug therapy; Animals; Dose-Response Relationship, Drug; Female; Ibogaine - analogs & derivatives; Ibogaine - pharmacology; Male; Nicotine - administration & dosage; Rats; Rats, Sprague-Dawley; Self Administration
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2016.10.010

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 45min. sessions. At weekly intervals they were administered by oral gavage doses of 18-MC (0, 10, 20 and 40mg/kg) following a repeated measures counterbalanced design twice. Acute oral 18-MC, at the 40mg/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 40mg/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) 6h/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.