TY - JOUR
T1 - Adenosine A2A receptor modulation affects the development of depressive-like behaviour and dopamine D2 receptor availability in rats exposed to repeated social defeat.
AU - Vazquez-Matias, Daniel A
AU - Henry, Samia
AU - Guerrin, Cyprien G J
AU - Prasad, Kavya
AU - Doorduin, Janine
AU - de Vries, Erik F J
N1 - Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2025/10/2
Y1 - 2025/10/2
N2 - 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.
AB - 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.
KW - Major depressive disorder
KW - Dopaminergic neurotransmission
KW - Dopamine D2 receptors
KW - A2A receptor modulation
KW - Repeated social defeat
U2 - 10.1016/j.pnpbp.2025.111540
DO - 10.1016/j.pnpbp.2025.111540
M3 - Article
C2 - 41135841
SN - 1878-4216
VL - 142
JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry
M1 - 111540
ER -