The antidepressant-like effect of guanosine involves the modulation of adenosine A 1 and A 2A receptors
Guanosine has been considered a promising candidate for antidepressant responses, but if this nucleoside could modulate adenosine A (A R) and A (A R) receptors to exert antidepressant-like actions remains to be elucidated. This study investigated the role of A R and A R in the antidepressant-like re...
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Published in | Purinergic signalling Vol. 19; no. 2; p. 387 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
01.06.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Guanosine has been considered a promising candidate for antidepressant responses, but if this nucleoside could modulate adenosine A
(A
R) and A
(A
R) receptors to exert antidepressant-like actions remains to be elucidated. This study investigated the role of A
R and A
R in the antidepressant-like response of guanosine in the mouse tail suspension test and molecular interactions between guanosine and A
R and A
AR 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 A
R and reduced A
R 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 A
R/A
R antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX - 2 mg/kg, i.p., a selective adenosine A
R 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 A
R antagonist). However, the antidepressant-like response of guanosine was completely abolished by adenosine (0.5 mg/kg, i.p., a non-selective adenosine A
R/A
R agonist), N-6-cyclohexyladenosine (CHA - 0.05 mg/kg, i.p., a selective adenosine A
receptor agonist), and N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA - 0.1 mg/kg, i.p., a selective adenosine A
receptor agonist). Finally, docking analysis also indicated that guanosine might interact with A
R and A
R at the adenosine binding site. Overall, this study reinforces the antidepressant-like of guanosine and unveils a previously unexplored modulation of the modulation of A
R and A
R in its antidepressant-like effect. |
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ISSN: | 1573-9546 |