Inhibiting NMDAR outside of the CNS is sufficient to induce arousal from hibernation: MK-801 (5 mg/kg; ip) induces arousal, indicated by an increase in the rate of O2 consumption (Vo2) and core body temperature (Tb) in a hibernating arctic ground squirrel (AGS) (a) while vehicle has no effect (b). Handling-induced arousal is shown for comparison (c). AP5 (5 mg/kg; ip), an NMDAR antagonist that does not cross the blood brain barrier, also induces arousal from hibernation (d). Arrowhead at 0.5h represents when drug (a, d) or vehicle (b, d) was delivered or arousal was initiated by handling (c). (From Jinka et al., 2012)