Effects of metabotropic glutamate 2/3 receptor antagonists in the stress-induced hyperthermia test in singly housed mice

Rationale The stress-induced hyperthermia (SIH) test in mice has been widely used as models including some physiological aspects of psychiatric disorders. Mediated by the autonomic nervous system, SIH is commonly known to occur both before and during exposure to stress-inducing or anxiogenic situations. Recently, modulation of the group II metabotropic glutamate (mGlu) 2/3 receptor has been proposed as a novel therapeutic approach for psychiatric disorders. Objectives In the present study, we evaluated the efficacy of selective mGlu2/3 receptor antagonists and an mGlu2/3 receptor agonist in the SIH test. Results mGlu2/3 receptor antagonists such as MGS0039 and LY341495 significantly and dose-dependently reduced SIH without affecting basal rectal temperatures. In contrast, mGlu2/3 receptor agonists such as MGS0008 were ineffective in the SIH test. The attenuation of SIH by MGS0039 was significantly blocked by pretreatment with WAY100635, a serotonin 1A receptor antagonist. In contrast, an AMPA receptor potentiator, CX546 failed to reduce the SIH. Conclusions Taken together, these results suggest that the blockade of mGlu2/3 receptor may prevent stress-induced autonomic hyperactivity, and that stimulation of the postsynaptic serotonin 1A receptor, but not AMPA receptor, may be involved in this action.