Deletion of Metabotropic Glutamate Receptors 2 and 3 (mGlu2 & mGlu3) in Mice Disrupts Sleep and Wheel-Running Activity, and Increases the Sensitivity of the Circadian System to Light

摘要: Sleep and/or circadian rhythm disruption (SCRD) is seen in up to 80% of schizophrenia patients. The co-morbidity and SCRD may part stem from dysfunction common brain mechanisms, which include the glutamate system, particular, group II metabotropic receptors mGlu2 mGlu3 (encoded by genes Grm2 Grm3). These are relevant pathophysiology potential treatment schizophrenia, have also been implicated sleep function. In present study, we characterised rhythms Grm2/3 double knockout (Grm2/3-/-) mice, provide further evidence for involvement regulation rhythms. We report several novel findings. Firstly, Grm2/3-/- mice demonstrated a decrease immobility-determined time an increase fragmentation. Secondly, showed heightened sensitivity effects light, manifested as increased period lengthening constant greater phase delays response nocturnal light pulses. Greater light-induced were exhibited wildtype C57Bl/6J following administration mGlu2/3 negative allosteric modulator RO4432717. results confirm photic entrainment pathways. Finally, diurnal wheel-running perturbed under standard light/dark cycle, but their rest-activity unaltered cages lacking running wheels, determined with passive infrared motion detectors. Hence, when assessing choice assay can major bearing on obtained.