Molecular Neurobiology

, Volume 53, Issue 1, pp 611–620 | Cite as

Role of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine

  • Carolina Gubert
  • Gabriel Rodrigo Fries
  • Bianca Pfaffenseller
  • Pâmela Ferrari
  • Robson Coutinho-Silva
  • Fernanda Bueno Morrone
  • Flávio Kapczinski
  • Ana Maria Oliveira Battastini
Article

Abstract

The objective of this study was to explore the association between the P2X7 purinergic receptor (P2X7R) and neuroinflammation using a preclinical model of acute bipolar mania. We analyzed the modulatory effects of P2X7R agonist (3′-O-(4-benzoyl)benzoyl-adenosine 5′-triphosphate, BzATP) and antagonists (brilliant blue, BBG and 3-[[5-(2,3 dichlorophenyl)-1H-tetrazol-1-yl]methyl]pyridine hydrochloride, A438079) on assessments related to behavior (locomotor activity), neuroinflammation (interleukin-1 beta, IL-1β; tumor necrosis factor alpha, TNF-α; and interleukin- 6, IL-6), oxidative stress (thiobarbituric acid reactive substances, TBARS) and neuroplasticity (brain-derived neurotrophic factor, BDNF) markers in a pharmacological model of mania induced by acute and chronic treatment with D-amphetamine (AMPH) (2 mg/kg) in mice. An apparent lack of responsiveness to AMPH was observed in terms of the locomotor activity in animals with blocked P2X7R or with genetic deletion of P2X7R in knockout (P2X7R−/−) mice. Likewise, P2X7R participated in the AMPH-induced increase of the proinflammatory and excitotoxic environment, as demonstrated by the reversal of IL-1β, TNF-α, and TBARS levels caused by P2X7R blocking. Our results support the hypothesis that P2X7R plays a role in the neuroinflammation induced by AMPH in a preclinical model of mania, which could explain the altered behavior. The present data suggest that P2X7R may be a therapeutic target related to the neuroinflammation reported in bipolar disorder.

Keywords

Bipolar disorder P2X7 receptor D-amphetamine Neuroinflammation 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Carolina Gubert
    • 1
    • 2
    • 3
  • Gabriel Rodrigo Fries
    • 2
    • 3
  • Bianca Pfaffenseller
    • 1
    • 2
    • 3
  • Pâmela Ferrari
    • 2
    • 3
    • 4
  • Robson Coutinho-Silva
    • 4
  • Fernanda Bueno Morrone
    • 5
  • Flávio Kapczinski
    • 2
    • 3
  • Ana Maria Oliveira Battastini
    • 1
    • 6
  1. 1.Programa de Pós-Graduação Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Bipolar Disorder Program and Laboratory of Molecular PsychiatryHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.INCT of Translational MedicinePorto AlegreBrazil
  4. 4.Instituto de Biofísica Carlos Chagas FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  5. 5.Instituto de Toxicologia e Farmacologia, Faculdade de FarmáciaPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  6. 6.Departamento de BioquímicaInstituto de Ciências Básicas da SaúdePorto AlegreBrazil

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