Related Experiment Video
Updated: Jan 4, 2026
Pentylenetetrazole-Induced Kindling Mouse Model
Published on: June 12, 2018
P2X7 receptor knockout mice display less aggressive biting behaviour correlating with increased brain activation in
Kristie Leigh Smith1, Stephanie M Todd1, Aurelie Boucher1
1Brain and Mind Centre, University of Sydney, Australia; Faculty of Medicine and Health, University of Sydney, Australia; Discipline of Pharmacology, University of Sydney, Australia.
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.
Insights
Mice lacking P2X7 receptors showed less obsessive-compulsive disorder-like behavior and reduced aggression. This suggests P2X7 receptor could be a therapeutic target for mental health conditions.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- P2X7 receptors are linked to psychiatric disorders like depression and bipolar disorder.
- Gain-of-function mutations in P2X7 receptors may drive neuroinflammation in affective disorders.
- The specific role of P2X7 receptors in other mental health conditions and behaviors needs more research.
Purpose of the Study:
- To investigate the impact of P2X7 receptor deletion on social behavior, marble burying (an OCD model), and aggression in mice.
- To analyze microglial density and neuronal activation (c-Fos expression) in P2X7 receptor knockout mice.
Main Methods:
- Germline deletion of the P2rx7 gene in mice.
- Assessment of social and marble burying behaviors during adolescence.
- Evaluation of aggressive attack behavior in adult mice using the resident-intruder test.
- Quantification of microglial cell densities and c-Fos expression in brain tissue.
Main Results:
- P2rx7 knockout mice exhibited significantly reduced marble burying behavior, particularly in late adolescence/early adulthood.
- Adult P2rx7 knockout mice displayed decreased aggressive attack behavior.
- No changes in microglial cell densities were observed, but c-Fos expression was elevated in the piriform cortex of knockout mice.
Conclusions:
- The P2X7 receptor plays a role in regulating behaviors relevant to OCD and aggression.
- Elevated neuronal activation in the piriform cortex suggests a potential mechanism for altered behavior.
- The P2X7 receptor emerges as a potential novel therapeutic target for anxiolytic and anti-OCD treatments.
More Related Videos
11:47Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells
Published on: April 3, 2019
07:54Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors
Published on: May 10, 2015