e5NT inhibitor protects acute restraint stress-induced depression by regulating nucleoside release in mice.

Objectives To determine whether ecto-5 '-nucleotidase (e5NT) contributes to the release of adenosine and uridine and whether is establishes the role of e5NT in acute restraint stress-induced depression and anxiety-like behaviours in mice. Methods Acute restraint stress was induced to detect the level of nucleoside in the hippocampus. Mouse hippocampal brain proteins were isolated and subjected to Western blotting (WB) experiments to examine the protein expression levels of proteins that affect nucleoside release. Adenosine 5 '-(alpha,beta-methylene)diphosphate (APCP), an e5NT inhibitor, was intraventricularly injected to investigate the regulatory effect of e5NT on nucleoside levels and behavioural changes caused by acute restraint stress in mice. Key findings Acute restraint stress increased the level of extracellular adenosine and uridine levels in the hippocampus of mice and significantly increased the expression of extracellular nucleoside-metabolizing enzymes were significantly increased. By administering APCP, the increase in adenosine and uridine levels caused by acute restraint stress could be suppressed. APCP inhibited behavioural changes, which were induced by acute restraint stress. Conclusions These data suggest that acute restraint stress may alter extracellular adenosine and uridine levels content in the hippocampus of mice via e5NT, and thus, the inhibition of e5NT may improve the anxiety behaviour in mice. Therefore, e5NT may therefore be a potential therapeutic target for the treatment of anxiety in mice.