The role of adenosine receptors on cannabis addiction

Cannabis is the most commonly used illegal recreational substance worldwide. Tetrahydrocannabinol (THC), a substance found in cannabis, is known to create anxiety-like behaviors and addiction, and affect cognitive processes. In recent years, it has been suggested that the adenosinergic system is important in the formation of addiction to a variety of stimulant substances. In our research, we investigated whether the adenosinergic system contribute to cannabis addiction in mice. For that purpose, THC (10mg/kg intraperitoneal, i.p), Adenosine A2A receptor agonist CGS (2.5 mg/kg subcutaneous, s.c.), Adenosine A2A receptor antagonist Istradefylline (3 mg/kg s.c.), THC+Istradefylline, and THC+CGS 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. On the days of the injections, the body weight changes of all groups were assessed. The open field and elevated plus maze tests were used to examine locomotor activity and anxiety-like behaviors after the injections were completed on the fifth day. RT-PCR was used to assess the levels of CB1 and adenosine A2A gene expression in hippocampal tissues. In our study, THC and CGS decreased mice's locomotor activity while increasing anxiety-like behavior. Istradefylline boosted locomotor activity while reducing anxiety-like behavior. In hippocampal tissues, THC and Istradefylline increased adenosine A2A gene expression while CGS decreased it. Co-administration of THC with the adenosine A2A receptor antagonist istradefylline or the adenosine A2A receptor agonist CGS decreased adenosine A2A gene expression. However changes in CB1 gene expression were not statistically significant in any group. The results suggest that adenosine A2A receptors may modulate the locomotor activity and anxiety-like behaviors in the mice treated with THC.