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 A 2A receptor modulation on the susceptibility to develop of depressive-like phenotype and the dopamine D 2 receptor availability, in rats exposed to repeated social defeat.

METHODS: 38 rats were divided into three groups which received vehicle, the A 2AR agonist CGS21680 (0.1 mg/kg), or the A 2AR 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. D 2 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 D 2 receptor availability in the striatum, in particular in caudate-putamen. A 2AR antagonist treatment also decreased D 2 receptor availability in the nucleus-accumbens.

CONCLUSION: Our study showed that the treatment with either an A 2AR agonist or an A 2AR antagonist prevented the development of depressive-like behaviour, and reduced the availability of D 2 receptor in the striatum after exposure to RSD most likely by modulating the receptor affinity.