Effects of Voluntary Ingestion of Synthetic Delta-9-Tetrahydrocannabinol on the Hedonic Value of Rewarding and Aversive Substances and CB1 Receptor Expression.

Abstract

Background: Human studies indicate a relationship between delta-9-tetrahydrocannabinol (THC) and alcohol use, yet research on their codependency remains limited. Rodent models have shown that cannabinoids can enhance the incentive salience and hedonic value of sucrose and alcohol. However, results seem to vary by the functions of THC dose and route of administration.

Materials and methods: The present study addresses these discrepancies by using a translational model of THC consumption, using lower oral doses of synthetic THC (Dronabinol). Male Long-Evans (n = 24) rats consumed a vehicle or THC-containing cookie (0.05 mg/kg or 0.5 mg/kg) before testing the palatability of rewarding and aversive substances in the taste reactivity paradigm.

Results: Separate, linear, mixed-effect models revealed that THC dose-dependently increased hedonic reactions to both sucrose (0.1 M and 0.5 M) and alcohol (10% and 40% ETOH) compared with control. Comparatively, THC reduced aversion to alcohol (10% and 40%) and quinine compared with vehicle. Western blot data analyzed via one-way Analysis of Variance (ANOVA) followed by Tukey's post hoc analysis revealed that repeated oral THC consumption dose-dependently downregulated cannabinoid receptor 1 receptor expression in the dorsal hippocampus, while no significant changes were observed in the nucleus accumbens or amygdala. Conclusions:These findings suggest that oral THC enhances the hedonic value of rewarding and aversive substances and provide insights into the neurobiological mechanisms that may contribute to the bidirectional use of cannabis and alcohol.