Involvement of Adenozine A2a Receptors in Anxiety-like Behaviors in Tetrahydrocannabinol Treated Mice

Abstract

Abstract Previous studies have suggested that adenosinergic system in the central nervous system (CNS), may play a role in both behavioral changes and the physiopathology of addiction induced by THC, and this is thought to be mediated by adenosine A2A receptors (A2AR). However, contribution of adenosinergic system isn’t well understood. In this study, we aimed to investigate the possible role of the adenosinergic system in THC-treated mice. For that purpose, THC (10 mg kg− 1), Adenosine A2AR agonist CGS-21680 (2.5 mg kg− 1), Adenosine A2AR antagonist Istradefylline (3 mg kg− 1), THC + Istradefylline, and THC + CGS-21680 were all given to male Swiss albino mice, once daily for five days. The same methods were used to administer the drug solvents to the sham groups. Anxiety-like behaviors were examined through the open field (OF) and elevated plus maze (EPM) tests in all groups. The expression levels of cannabinoid CB1R and adenosine A2AR genes in hippocampal tissues were assessed using real-time PCR (qPCR). THC treatment decreased the frequency of center crossings and rearing behavior in the OF test. In the EPM test, there was a notable decrease in the time spent in the open arm, alongside an increase in the time spent in the closed arm. Similar effects were obtained by the administration of CGS-21680 or THC + CGS-21680. Conversely istradefylline significantly prevented THC-induced anxiety-like behaviors. Also, THC caused a significant increase in the expression of adenosine A2AR genes in hippocampal tissues, while resulting in a partial decrease in CB1R expression. These results suggest that adenosine A2AR has a potential role in anxiety-like behaviors in THC-treated mice.