期刊
BEHAVIOURAL BRAIN RESEARCH
卷 198, 期 1, 页码 83-90出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2008.10.018
关键词
P2X(7) receptor; P2X(7) receptor KO mice; Depression; Anxiety; Pro-inflammatory cytokines
资金
- Abbott Laboratories
The purinergic P2X(7) receptor is a ligand-gated ion channel found on peripheral macrophages and microglia in the nervous system. Activation of P2X(7) receptors results in the rapid release of interleukin-1 beta (IL-1 beta). Cytokines like IL-1 beta are suggested to be involved in the pathophysiology of depression. The aim of this study was to behaviorally profile P2X(7) receptor knockout (KO) mice in behavioral models of depression- and anxiety-like behaviors. P2X(7) receptor KO and wild type (WT) mice were tested in multiple models including; forced swim test, tail suspension test, elevated plus maze, novelty suppressed feeding, spontaneous locomotor activity, and food intake. P2X7 receptor KO mice exhibited an antidepressant-like profile in tail suspension test and forced swim test; an effect that was not associated with changes in spontaneous locomotor activity. In addition, P2X(7) receptor KO mice showed higher responsivity to a subefficacious dose of the antidepressant drug imipramine (15 mg/kg) in forced swim test. No significant differences between genotypes were observed in models of anxiety. These data support the relevance of pro-inflammatory cytokines in depressive-like states, and suggest that P2X7 receptor antagonists could be of potential interest for the treatment of affective disorders. (C) 2008 Elsevier B.V. All rights reserved.
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