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

The purinergic P2X7 receptor is a ligand-gated ion channel found on peripheral macrophages and microglia in the nervous system. Activation of P2X7 receptors results in the rapid release of interleukin-1β (IL-1β). Cytokines like IL-1β are suggested to be involved in the pathophysiology of depression. The aim of this study was to behaviorally profile P2X7 receptor knockout (KO) mice in behavioral models of depression- and anxiety-like behaviors. P2X7 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, P2X7 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.