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Article ; Online: Reduced P2X receptor levels are associated with antidepressant effect in the learned helplessness model

Deidiane Elisa Ribeiro / Plinio C. Casarotto / Laura Staquini / Maria Augusta Pinto e Silva / Caroline Biojone / Gregers Wegener / Samia Joca

PeerJ, Vol 7, p e

2019  Volume 7834

Abstract: Purinergic receptors, especially P2RX, are associated to the severity of symptoms in patients suffering from depressive and bipolar disorders, and genetic deletion or pharmacological blockade of P2RX7 induces antidepressant-like effect in preclinical ... ...

Abstract Purinergic receptors, especially P2RX, are associated to the severity of symptoms in patients suffering from depressive and bipolar disorders, and genetic deletion or pharmacological blockade of P2RX7 induces antidepressant-like effect in preclinical models. However, there is scarce evidence about the alterations in P2RX7 or P2RX4 levels and in behavioral consequences induced by previous exposure to stress, a major risk factor for depression in humans. In the present study, we evaluated the effect of imipramine (IMI) on P2RX7 and P2RX4 levels in dorsal and ventral hippocampus as well as in the frontal cortex of rats submitted to the pretest session of learned helplessness (LH) paradigm. Repeated, but not acute administration of IMI (15 mg/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/P2RX4 antagonist brilliant blue G (BBG: 25 or 50 mg/kg ip) on the LH paradigm. We observed that repeated (7 days) but not acute (1 day) treatment with BBG (50 mg) reduced the number of failures to escape the shocks in the test session, a parameter mimicked by the same regimen of IMI 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 LH paradigm after repeated drug administration.
Keywords P2X7 receptor ; P2X4 receptor ; Learned helplessness ; Brilliant blue G ; Imipramine ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code 150
Language English
Publishing date 2019-10-01T00:00:00Z
Publisher PeerJ Inc.
Document type Article ; Online
Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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