鸟苷被认为是抗抑郁反应的有希望的候选者,但是,如果该核苷可以调节腺苷A1(A1R)和A2A(A2AR)受体以发挥抗抑郁样作用,则仍有待阐明。本研究通过对接分析研究了A1R和A2AR在小鼠尾部悬吊试验中鸟苷类抗抑郁反应中的作用以及鸟苷与A1R和A2AR之间的分子相互作用。急性(60分钟)给予鸟苷(0.05mg/kg,p.o.)显着减少了尾部悬挂测试中的不动时间,在不影响开场试验中的运动性能的情况下,表明有抗抑郁作用.这种行为反应与海马中A1R增加和A2AR免疫含量降低平行,但不是在前额叶皮层,老鼠。咖啡因预处理不会改变鸟苷介导的抗抑郁作用(3mg/kg,i.p.,非选择性腺苷A1R/A2AR拮抗剂),8-环戊基-1,3-二丙基黄嘌呤(DPCPX-2mg/kg,i.p.,选择性腺苷A1R拮抗剂),或4-(2-[7-氨基-2-{2-呋喃基}{1,2,4}三唑-{2,3-a}{1,3,5}三嗪-5-基-氨基]乙基)-苯酚(ZM241385-1mg/kg,i.p.,选择性腺苷A2AR拮抗剂)。然而,腺苷完全消除了鸟苷的抗抑郁样反应(0.5mg/kg,i.p.,一种非选择性腺苷A1R/A2AR激动剂),N-6-环己基腺苷(CHA-0.05mg/kg,i.p.,选择性腺苷A1受体激动剂),和N-6-[2-(3,5-二甲氧基苯基)-2-(甲基苯基)乙基]腺苷(DPMA-0.1mg/kg,i.p.,选择性腺苷A2A受体激动剂)。最后,对接分析还表明,鸟苷可能在腺苷结合位点与A1R和A2AR相互作用。总的来说,这项研究加强了鸟苷的抗抑郁样作用,揭示了A1R和A2AR在抗抑郁样作用中的一个以前未被研究过的调节.
Guanosine has been considered a promising candidate for antidepressant responses, but if this nucleoside could modulate adenosine A1 (A1R) and A2A (A2AR) receptors to exert antidepressant-like actions remains to be elucidated. This study investigated the role of A1R and A2AR in the antidepressant-like response of guanosine in the mouse tail suspension test and molecular interactions between guanosine and A1R and A2AR by docking analysis. The acute (60 min) administration of guanosine (0.05 mg/kg, p.o.) significantly decreased the immobility time in the tail suspension test, without affecting the locomotor performance in the open-field test, suggesting an antidepressant-like effect. This behavioral response was paralleled with increased A1R and reduced A2AR immunocontent in the hippocampus, but not in the prefrontal cortex, of mice. Guanosine-mediated antidepressant-like effect was not altered by the pretreatment with caffeine (3 mg/kg, i.p., a non-selective adenosine A1R/A2AR antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX - 2 mg/kg, i.p., a selective adenosine A1R antagonist), or 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)-phenol (ZM241385 - 1 mg/kg, i.p., a selective adenosine A2AR antagonist). However, the antidepressant-like response of guanosine was completely abolished by adenosine (0.5 mg/kg, i.p., a non-selective adenosine A1R/A2AR agonist), N-6-cyclohexyladenosine (CHA - 0.05 mg/kg, i.p., a selective adenosine A1 receptor agonist), and N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA - 0.1 mg/kg, i.p., a selective adenosine A2A receptor agonist). Finally, docking analysis also indicated that guanosine might interact with A1R and A2AR at the adenosine binding site. Overall, this study reinforces the antidepressant-like of guanosine and unveils a previously unexplored modulation of the modulation of A1R and A2AR in its antidepressant-like effect.