title: Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA. Electronic address: azadi@duke.edu.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Rezvani
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors.forename: Marty C
authors.initials: MC
authors.lastname: Cauley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Slade
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Wells
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, Albany Medical College, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Glick
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors.forename: Jed E
authors.initials: JE
authors.lastname: Rose
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000284:Administration, Oral; D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
chemical_list: D007050:Ibogaine; D009538:Nicotine; C103345:18-methoxycoronaridine
keywords: Addiction; Alcohol preferring rat; Alcoholism; Drinking; Smoking; Treatment