Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in rats.
Amir H Rezvani, Marty C Cauley, Susan Slade, Corinne Wells, Stanley D Glick, Jed E Rose, Edward D Levin
Pharmacology, biochemistry, and behavior 2016 DOI: 10.1016/j.pbb.2016.10.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Young adult female Sprague-Dawley rats (nicotine study) and male and female alcohol preferring (P) rats (alcohol study) |
| Intervention | 18-methoxycoronaridine (18-MC) |
| Dose | 0, 10, 20, and 40 mg/kg |
| Topics | Addiction |
| Keywords | Alcohol preferring rat Drinking Addiction treatment Alcoholism research Smoking cessation Novel compounds |
| Citations | 22 |
| Key findings | Oral 18-MC significantly reduced nicotine self-administration in female rats at 40 mg/kg and dose-dependently reduced alcohol intake in both male and female alcohol-preferring rats. |
Abstract
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.