P2X7 receptor knockout mice display less aggressive biting behaviour correlating with increased brain activation in the piriform cortex

Abstract

P2X7 receptors are implicated in the pathophysiology of psychiatric conditions such as depression and bipolar disorder. P2X7 receptors regulate the release of pro-inflammatory cytokines from microglia, and gain-of-function P2X7 mutations may contribute to the neuroinflammation found in affective disorders. However, the role of this receptor in mediating other mental health conditions and aberrant behaviours requires further examination. The current study we investigated the effects of germline genetic deletion of P2xr7 on social and marble burying behaviours in mice throughout the critical adolescent developmental period. Marble burying behaviour is thought to provide a mouse model of obsessive-compulsive disorder (OCD). We also characterised the effects of P2rx7 deletion on aggressive attack behaviour in adult mice and subsequently quantifieded microglial cell densities and c-Fos expression, a marker of neuronal activation. P2rx7 knockout mice displayed reduced OCD-related marble burying behaviour which was most pronounced in late adolescence/early adulthood. P2rx7 knockout mice also exhibited reduced aggressive attack behaviours in adulthood in the resident-intruder test. Reduced aggression in P2xr7 knockout mice did not coincide with changes to microglial cell densities, however c-Fos expression was elevated in the piriform cortex of P2rx7 knockout mice compared to wildtype mice. This study suggests that the P2X7 receptor might serve as a novel target for serenic or anti−OCD therapeutics.