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

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 A _2A receptors (A _2A R). 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 A _2A R agonist CGS-21680 (2.5 mg kg ^− 1 ), Adenosine A _2A R 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 CB ₁ R and adenosine A _2A R 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 A _2A R genes in hippocampal tissues, while resulting in a partial decrease in CB ₁ R expression. These results suggest that adenosine A _2A R has a potential role in anxiety-like behaviors in THC-treated mice.