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. 2009 Mar 2;198(1):83-90.
doi: 10.1016/j.bbr.2008.10.018. Epub 2008 Oct 18.

Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders

Ana M Basso  1 , Natalie A Bratcher, Richard R Harris, Michael F Jarvis, Michael W Decker, Lynne E Rueter
Affiliations

Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders

Ana M Basso et al. Behav Brain Res. .

Abstract

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. P2X(7) 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 P2X(7) receptor antagonists could be of potential interest for the treatment of affective disorders.

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