Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders.
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.
Basso
Ana M
AM
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. Ana.basso@abbott.com
Bratcher
Natalie A
NA
Harris
Richard R
RR
Jarvis
Michael F
MF
Decker
Michael W
MW
Rueter
Lynne E
LE
D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000276:immunology / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003863:Depression / Q000276:immunology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004435:Eating; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000502:physiology; D019417:Hindlimb Suspension / Q000502:physiology; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology; D053583:Interleukin-1beta / Q000032:analysis; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D016133:Polymerase Chain Reaction; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics*; D013550:Swimming
D000929:Antidepressive Agents, Tricyclic; D053583:Interleukin-1beta; D018048:Receptors, Purinergic P2; D007099:Imipramine