Peer Review #1 of "Reduced P2X receptor levels are associated with antidepressant effect in the learned helplessness model (v0.2)"

Abstract

In the present study, we evaluated the effect of imipramine on P2RX7 and P2RX4 levels in dorsal/ventral hippocampus and frontal cortex of rats submitted to the pretest session of learned helplessness paradigm. Repeated, but not acute administration of imipramine (15mg/kg ip) reduced the levels of both P2RX7 and P2RX4 in the ventral, but not in dorsal hippocampus or frontal cortex. In addition, we tested the effect of P2RX7/X4 antagonist brilliant blue G (BBG: 25 or 50mg/kg ip) on the learned helplessness paradigm. We observed that repeated (7 days) but not acute (1 day) treatment with BBG (50mg) reduced the number of failures to escape the shocks in the test session, a parameter mimicked by the same regimen of imipramine treatment. Taken together, our data indicates that pharmacological blockade or decrease in the expression of P2RX7 is associated to the antidepressant-like behavior observed in the learned helplessness paradigm after repeated drug administration.