Effects of voluntary ingestion of delta-9-tetrahydrocannabinol on the hedonic value of rewarding and aversive substances

Abstract

Human studies indicate a relationship between [Delta]-9-tetrahydrocannabinol (THC) and alcohol use, yet research on their co-dependency remains limited. Rodent models have shown that cannabinoids can enhance the incentive salience and hedonic value of sucrose and alcohol, but results vary, especially with high doses of THC. This study addresses these discrepancies by using a translational model with lower, human-relevant doses of synthetic THC (Dronabinol). Male Long-Evans rats consumed either a vehicle or THC-containing (0.5 mg/kg) cookie before testing in a taste reactivity paradigm. Results show that THC increased hedonic reactions to both sucrose (0.1M & 0.5M) and alcohol (10% & 40% ETOH) compared to control. Comparatively, THC reduced aversion to alcohol (10% & 40%) and quinine. THC dose dependently downregulated cannabinoid receptor 1 receptor expression in the dorsal hippocampus and increased pERK expression in the same region, while no significant changes were observed in the Nucleus Accumbens or Amygdala. 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 co-morbidity of alcohol and THC use disorders.