Reduced P2X receptor levels are associated with antidepressant effect in the learned helplessness model

PeerJ

article

Deidiane Elisa Ribeiro¹  Plinio C. Casarotto⁴  Laura Staquini¹  Maria Augusta Pinto e Silva⁵  Caroline Biojone⁴  Gregers Wegener²  Samia Joca⁵ 

[1] Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo;Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University;Department of Biochemistry, Chemistry Institute, University of São Paulo;Neuroscience Center—HILIFE, University of Helsinki;Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo;Aarhus Institute of Advanced Studies ,(AIAS), Aarhus University

关键词: P2X7 receptor;    P2X4 receptor;    Learned helplessness;    Brilliant blue G;    Imipramine;   

DOI  :  10.7717/peerj.7834

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY