Involvement of Adenosine A2A receptors in anxiety-like behaviors in tetrahydrocannabinol-treated mice

Abstract

Background: Previous studies have suggested that adenosinergic system in the central nervous system may play a role in both behavioral changes and the physiopathology induced by Δ9-tetrahydrocannabinol (THC), and this is thought to be mediated by adenosine A2A receptors(A2ARs). However, the contribution of the adenosinergic system to the anxiety-like behaviorsin response to THC in mice is not well understood. Aims: In this study, we aimed to investigate the possible role of the adenosinergic system in THC-treated mice. Methods: For that purpose, we combined behavioral tests and molecular analyses to investigate the effects of THC in relation with the agonist and antagonist of the adenosinergic system, CGS-21680 (CGS) and istradefylline,respectively, on both anxiety-like behaviors and hippocampal gene expression. Results: The results demonstrated that THC induced anxiety-like behavior, and gene expression patterns indicated a significant interaction between the adenosinergic and cannabinoidergic systems. Notably, the data suggest that THC plays a predominant role in this molecular interplay, with its effects being partially modulated by changes in the expression of both cannabinoidergic and adenosinergic receptors, CB1R and A2AR, respectively. Conclusion: These findings contribute to the understanding of THC’s complex pharmacological actions, highlighting the importance of receptor cross talk in modulating anxiety and other behavioral outcomes.