Role of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine
Autor: | Gabriel Rodrigo Fries, Robson Coutinho-Silva, Flávio Kapczinski, Ana Maria Oliveira Battastini, Bianca Pfaffenseller, Carolina Gubert, Pâmela Ferrari, Fernanda Bueno Morrone |
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Rok vydání: | 2014 |
Předmět: |
0301 basic medicine
Agonist Male Bipolar Disorder Dextroamphetamine Purinergic Antagonists medicine.drug_class Neuroscience (miscellaneous) Pharmacology Thiobarbituric Acid Reactive Substances Proinflammatory cytokine 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Neurotrophic factors medicine TBARS Animals Amphetamine Neuroinflammation Mice Knockout Chemistry Purinergic receptor Brain Mice Inbred C57BL Disease Models Animal 030104 developmental biology Neurology Purinergic Agonists Mice Inbred CBA Receptors Purinergic P2X7 medicine.symptom Inflammation Mediators Mania Neuroscience 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Molecular neurobiology. 53(1) |
ISSN: | 1559-1182 |
Popis: | 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. |
Databáze: | OpenAIRE |
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