Role of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine
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- 作者：Carolina Gubert ; Gabriel Rodrigo Fries ; Bianca Pfaffenseller…
- 关键词：Bipolar disorder ; P2X7 receptor ; D ; amphetamine ; Neuroinflammation
- 刊名：Molecular Neurobiology
- 出版年：2016
- 出版时间：January 2016
- 年：2016
- 卷：53
- 期：1
- 页码：611-620
- 全文大小：633 KB
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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. Programa de Pós-Graduação Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil
2. Bipolar Disorder Program and Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, 90035-003, Brazil
3. INCT of Translational Medicine, Porto Alegre, Brazil
4. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil
5. Instituto de Toxicologia e Farmacologia, Faculdade de Farmácia, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, 90619-900, Brazil
6. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos, 2600–anexo, CEP, Porto Alegre, RS, 90035-003, Brazil - 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
- 出版者：Springer US
- ISSN：1559-1182
文摘
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.