THE INFLUENCE OF CAFFEINE CONSUMPTION ON EXPRESSION OF CB1 AND CB2 CANNABINOID RECEPTORS IN ANIMAL MODELS OF ANXIETY

Background: Anxiety disorders are the most prevalent mental health problem. Animal models have been developed to elucidate the molecular mechanisms underlying this behavior and to develop new therapeutic strategies. In this context, the endocannabinoid system emerges as a promise, since recent studies already show its participation in the etiology of psychiatric disorders. Besides that, caffeine is the most consumed psychoactive drug and can modulate anxiety behaviors. 

Objective: The purpose of this study was to compare the content of CB1 and CB2 receptors in the hippocampus of two strains of male Wistar rats selected by their freezing behavior. Furthermore, we also investigated if chronic caffeine intake could alter anxiety behavior, by modulating the CB1 and CB2 expression.

Methodology: Carioca High-conditioned Freezing (CHF) and Carioca Low-conditioned Freezing (CLF) rats were bred based on differences in their freezing behavior in response to a conditioned context and were compared with control animals. All the animal procedures were approved by the Local Animal Care Committee of CEUA UFF (protocol no. 1707150622) and the samples were processed for Western Blot and immunofluorescence techniques. 

Results: Behavioral analysis confirmed the highest freezing rates for CHF and the lowest for CLF. The analysis revealed that the CHF animals have the lowest content of CB1 receptor in the ventral hippocampus. Also, caffeine consumption seems to decrease CB1 expression in all groups. Concerning CB2 receptor, CLF and control rats seem to present lower levels compared to the CHF group and caffeine ingestion does not seem to alter CB2 expression. 

Conclusion: These data suggest that the differential expression of CB1 and CB2 receptors may be involved in behavioral responses related to anxiety in these animals. Furthermore, they suggest an interaction of the endocannabinoid and adenosinergic systems in the hippocampus, opening possible therapeutic strategies in the future.