| Abstract [eng] |
Alcohol Use Disorder (AUD) is defined by compulsive drinking and loss of control over con- sumption, affecting approximately 280 million people globally. Current pharmacological treatments provide only modest benefit. The endocannabinoid system, particularly CB1 receptors, modulates both the motivational and hedonic components of alcohol reinforcement. Two phytocannabinoids were evaluated: delta-9-tetrahydrocannabivarin (THCV), a neutral CB1 antagonist, and cannabidiol (CBD), a negative allosteric modulator of CB1. Sixty male Wistar rats (2-months-old) were given 6-8 months of continuous two-bottle choice access to water and 10% ethanol. The highest-drinking animals were transferred to optical lickometer chambers. Drinking microstructure (bout number, size, duration and lick rate) was analysed sepa- rately for alcohol and water using a custom Python script. A bout was defined as at least 20 licks with inter-lick intervals below 60 seconds. Each drug block comprised three baseline days, three treatment days, and two post-treatment days. THCV (vehicle 5% Tween 80, 5 mg/kg, 20 mg/kg) and CBD (vehicle 0.5% methylcellulose, 20 mg/kg, 40 mg/kg) were tested in separate blocks. Baseline microstructure confirmed that ethanol bout size, duration, and lick rate were signifi- cantly higher than water. Administration of THCV (5-20 mg/kg) significantly reduced total 24-hour ethanol intake in a dose-dependent manner without altering water consumption. Microstructure anal- ysis revealed that this reduction was not accompanied by a significant change in alcohol bout number, indicating that the motivational drive to initiate drinking was preserved. Instead, THCV trended to- ward reduced bout duration and significantly reduced bout size alongside increased water bout size and duration, suggesting a selective attenuation of within-bout hedonic reinforcement. CBD (20–40 mg/kg) similarly reduced daily ethanol consumption. However, in contrast to THCV, CBD-treated animals did not exhibit a pronounced reduction in alcohol bout duration or size but reduced ethanol licking rate. These divergent microstructural trends suggest that THCV and CBD may engage disso- ciable mechanisms in the regulation of voluntary alcohol consumption, supporting their further in- vestigation as candidate pharmacotherapies for AUD. |
