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

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  • Deidiane Elisa Ribeiro, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil., Department of Biochemistry, Chemistry Institute, University of Sao Paulo, Sao Paulo SP 05508-000, Brazil. deidiane@hotmail.com.
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  • Plinio C Casarotto, School of Medicine, Campus USP, Ribeirão Preto, SP 14049-900, Brazil; Neuroscience Center - HILife, University of Helsinki, Finland.
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  • Laura Staquini, Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
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  • Maria Augusta Pinto E Silva, Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto 14040-903, Brazil. aline.roncalho@gmail.com.
  • ,
  • Caroline Biojone, School of Medicine, Campus USP, Ribeirão Preto, SP 14049-900, Brazil; Neuroscience Center - HILife, University of Helsinki, Finland.
  • ,
  • Gregers Wegener
  • Samia Joca

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.

Original languageEnglish
Article numbere7834
JournalPeerJ
Volume7
ISSN2167-8359
DOIs
Publication statusPublished - 2019

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© 2019 Ribeiro et al.

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