Using telemetry to measure stress-induced hyperthermia in metabotropic glutamate receptor 5 knockout mice
D. Brodkin, M. Bradbury, N. Warren, L. Bristow and M. Varney
Behavioral Pharmacology, Merck, San Diego, California, U.S.A.
Stress-induced hyperthermia (SIH) in mice is sensitive to anxiolytic properties of drugs. In this paradigm, stress causes a mild increase in body temperature that can be blocked by anxiolytic drugs [1]. Recently, the selective and systemically active antagonist for the metabotropic glutamate receptor 5 (mGluR5), MPEP (2-methyl-6-(phenylethynyl)pyridine), was reported to produce anxiolytic-like activity in a number of rodent models of anxiety, including stress-induced hyperthermia in mice [2]. It is often suggested that genetically modified mice lacking a particular receptor may provide a useful tool for predicting the effects of compounds that act at that receptor.
We tested this hypothesis for the mGluR5 receptor by examining mice genetically modified to lack the mGluR5 receptor (mGlur5-KO) in several variations of the SIH procedure. We employed classical SIH, using rectal measurement of body temperature, and radiotelemetric measurement of body temperature, in response to saline injection or the introduction of an intruder into the home cage (Data Sciences International mouse temperature and physical activity telemetry units model #TA10TA-F20, Dataquest A.R.T.; St. Paul, MN). The mGluR5-KO mice displayed a significant attenuation of the hyperthermic response to stress compared to wild-type (WT) controls.
That the mGluR5-KO mice displayed this anxiolytic-like phenotype suggests that mGluR5 antagonists may be useful in the treatment of anxiety. Furthermore, these findings parallel the effects of MPEP on SIH and add support to the notion that knockout animals may be useful tools for predicting the effects of antagonists.
References
Paper presented at Measuring Behavior 2002 , 4th International Conference on Methods and Techniques in Behavioral Research, 27-30 August 2002, Amsterdam, The Netherlands