The Effects of the α3β4 Nicotinic Acetylcholine Receptor Antagonist, 18-Methoxycoronaridine (18-MC), on Alcohol-Related Behaviors

Open Access
Author:
Ruggery, Colton
Area of Honors:
Biobehavioral Health
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Helen Marie Kamens, Thesis Supervisor
  • Helen Marie Kamens, Honors Advisor
  • David John Vandenbergh, Faculty Reader
Keywords:
  • 18-Methoxycoronaridine
  • 18-MC
  • Nicotinic Acetylcholine Receptor
  • nAChR
  • Alcohol
  • Alcohol Addiction
  • Mice
  • Binge Drinking
  • α3β4
  • alpha3beta4
  • Loss of Righting Reflex
  • Alcohol Metabolism
  • Drinking in the Dark
  • Locomotor Activity
  • Ethanol
  • Antagonist
  • Ibogaine
  • Alcohol Use Disorder
Abstract:
A major issue in the United States today is the prevalence of alcohol addiction and binge alcohol consumption. Binge drinking can lead to alcohol dependence, and while there are approved drugs to help treat alcoholics, these drugs are mostly ineffective or have unwanted side effects. However, a new drug with anti-addictive properties, 18-Methoxycoronaridine (18-MC), has potential to one day be used in clinical settings as a therapeutic tool. 18-MC is an α3β4 nicotinic acetylcholine receptor (nAChR) antagonist that has been shown to reduce alcohol self-administration, and other abused drugs. However, we know of no research that has examined the effect of 18-MC on binge alcohol consumption and other alcohol-related behaviors. The current study investigated 18-MC’s efficacy in reducing alcohol consumption in C57BL/6J male and female mice. It also determined the effect that 18-MC has on basal locomotor activity in addition to alcohol’s sedative-hypnotic properties and alcohol metabolism. Finally, the study determined whether or not 18-MC can be considered a specific treatment for alcohol by testing its effect on saccharin consumption. The results determined that 18-MC reduced ethanol consumption in male and female mice while having no effect on saccharin consumption. There were no effects observed on the ethanol-induced sedation or metabolism. Locomotor sedating effects were observed for high doses of 18-MC in male and female mice, but these effects were brief. The results of this study provide evidence of 18-MC’s efficacy in reducing alcohol consumption in mice by antagonizing α3β4 nAChRs while having little effect on other alcohol-related behaviors. Further research on the underlying mechanisms behind 18-MC’s actions should be conducted in order to determine its potential as a clinical anti-addiction drug.