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

Author(s)

Ribeiro, Deidiane Elisa ^{[1, 2, 3]} ; Casarotto, Plinio C. ^[4] ; Staquini, Laura ^[1] ; Pinto e Silva, Maria Augusta ^[5] ; Biojone, Caroline ^[4] ; Wegener, Gregers ^[2] ; Joca, Samia ^{[5, 6]}

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto - Brazil

^[2] Aarhus Univ, Dept Clin Med, Translat Neuropsychiat Unit, Aarhus - Denmark

^[3] Univ Sao Paulo, Chem Inst, Dept Biochem, Sao Paulo - Brazil

^[4] Univ Helsinki, Neurosci Ctr HILife, Helsinki - Finland

^[5] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto - Brazil

^[6] Aarhus Univ, AIAS, Aarhus - Denmark

• Document type: Journal article
• Source: PeerJ; v. 7, OCT 21 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 13/01737-7 - Purinergic system involvement in the behavioral consequences of stress and in the antidepressant mechanism of action
• Grantee: Deidiane Elisa Ribeiro
• Support Opportunities: Scholarships in Brazil - Doctorate