Involvement of Adenosine A 2 A 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 Δ 9 ‐tetrahydrocannabinol (THC), and this is thought to be mediated by adenosine A 2 A receptors (A 2 ARs). However, the contribution of the adenosinergic system to the anxiety‐like behaviors in 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, CB 1 R and A 2 AR, 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.