INFLUENCE OF A2A TREATMENT ON DEPRESSIVE‑LIKE BEHAVIOR AND D2‑RECEPTOR AVAILABILITY IN RATS EXPOSED TO REPEATED SOCIAL DEFEAT

The interaction between the dopaminergic and adenosinergic systems in depressive phenotypes remains largely unexplored. This study aimed to investigate the effect of adenosine A2a receptor modulation on the development of depressive-like behavior and dopamine D2 receptor availability, in rats exposed to repeated social defeat. Thirty-eight rats were divided into three groups which received vehicle, the A2A agonist CGS21680 (0.1 mg/kg), or the A2A antagonist KW6002 (1 mg/kg). Rats underwent 5 days of repeated social defeat using the resident intruder paradigm. Anhedonia-like and anxiety-like behavior were assessed using a sucrose preference and open field tests respectively to validate the depressive-like phenotype. D2 receptor availability in the striatal regions was assessed using [11C]raclopride-PET. Treatment with both CGS21680 and KW6002 prevented a decrease in sucrose preference and decreased locomotor activity after social defeat. Both drugs decreased D2 receptor availability in the striatum, in particular in caudate-putamen. A2AR-antagonist treatment also decreased it D2 receptor availability in the nucleus-accumbens. Our study showed that the treatment with either an A2AR agonist or an A2AR antagonist prevented the development of depressive-like behavior, and reduced the availability of D2R in the striatum after exposure to RSD.