Reduced stress-induced hyperthermia in mGluR5 knockout mice

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Metabotropic glutamate receptor subtype 5 (mGluR5) involvement in anxiety is suggested by anxiolytic effects of mGluR5 antagonists.
• Stress-induced hyperthermia (SIH) is a rodent model for anxiety, where stress elevates body temperature, and anxiolytics can block this response.

Purpose of the Study:

• To investigate the role of mGluR5 in anxiety expression.
• To examine the stress response in mGluR5-knockout mice using SIH paradigms.

Main Methods:

• Utilized three variations of the SIH procedure: classical SIH, radiotelemetric measurement after saline injection, and radiotelemetric measurement in response to intruder stress.
• Compared stress-induced hyperthermia in mGluR5-knockout mice and their wild-type littermates.
• Administered the selective mGluR5 antagonist MTEP to both wild-type and mGluR5-knockout mice to confirm findings.

Main Results:

• mGluR5-knockout mice exhibited a significantly attenuated hyperthermic response to stress across all three SIH procedures compared to wild-type controls.
• MTEP administration reduced SIH in wild-type mice but had no effect in mGluR5-knockout mice.
• These results indicate an anxiolytic-like phenotype in mGluR5 knockout mice and confirm the specificity of MTEP's anxiolytic-like effect.

Conclusions:

• The findings strongly support a role for mGluR5 in the expression of anxiety.
• mGluR5 knockout mice display an anxiolytic-like phenotype.
• Selective mGluR5 antagonists, like MTEP, may represent a viable therapeutic strategy for anxiety disorders.