Alcohol use disorder (AUD) is a leading cause of preventable death in the United States, however existing treatments are ineffective and produce aversive side effects such as nausea and fatigue. One potential therapeutic for AUD is the α3β4 nicotinic acetylcholine receptor (nAChR) antagonist 18- methoxycoronaridine (18-MC). Prior work has shown that 18-MC reduces ethanol consumption in rodent models. The present study sought to further examine the therapeutic potential of 18-MC by testing its effects on nonconsummatory behaviors. We examined 2 behavioral measures: ethanol-induced locomotor stimulation, which measures euphoric properties of the drug, and the expression of locomotor sensitization which models neuroadaptations in response to repeated exposure. We tested dose-dependent effects of 18-MC (0, 10, 20 and 30 mg/kg) administration on ethanol stimulation and locomotor sensitization in female and male DBA/2J mice. 18-MC had no effect on acute ethanol-induced stimulation, but the highest dose (30 mg/kg) significantly decreased the expression of locomotor sensitization. Our results support the involvement of α3β4 nAChR in the expression of ethanol-induced locomotor sensitization and suggest that 18-MC may be a therapeutic for AUD.
All Science Journal Classification (ASJC) codes
- Psychiatry and Mental health
- Pharmacology (medical)