Adenosine A2A receptor modulation affects the development of depressive-like behaviour and dopamine D2 receptor availability in rats exposed to repeated social defeat.

UNLABELLED: 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 susceptibility to develop of depressive-like phenotype and the dopamine D2 receptor availability, in rats exposed to repeated social defeat.

METHODS

38 rats were divided into three groups which received vehicle, the A2AR agonist CGS21680 (0.1 mg/kg), or the A2AR antagonist KW6002 (1 mg/kg). Rats underwent 5 days of repeated social defeat (RSD) using the resident intruder paradigm. Anhedonia-like and anxiety-like behaviour were assessed using the sucrose preference test and open field test respectively to validate the depressive-like phenotype. D2 receptor availability in the striatal regions was assessed using [11C]raclopride-PET.

RESULTS

Treatment with both CGS21680 and KW6002 prevented a decrease in sucrose preference, whereas the treatment with CGS21680 also 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 D2 receptor availability in the nucleus-accumbens.

CONCLUSION

Our study showed that the treatment with either an A2AR agonist or an A2AR antagonist prevented the development of depressive-like behaviour, and reduced the availability of D2 receptor in the striatum after exposure to RSD most likely by modulating the receptor affinity.