Neurobehavioral Consequences of the 5′-AMP-Induced Torpor-like Hypothermic State

Torpor is a hypometabolic and hypothermic state that enables survival under extreme energetic constraints. Pharmacological induction with 5′-AMP produces a controllable torpor-like hypothermic state with hypometabolic features documented for this model, relevant to long-duration spaceflight. Such a state could mitigate the physiological hazards of deep-space missions, including cosmic radiation exposure and muscle wasting, and, by minimizing oxygen demand, preserve neural integrity and enhance radiation tolerance. However, translational application requires confirmation that induced hypometabolism does not impair cognitive or behavioral function; this is especially pressing given evidence that the state causes reversible tau hyperphosphorylation at phospho-sites also altered in Alzheimer’s disease, but without tau aggregation. We subjected C57BL/6 mice to 5′-AMP combined with a mildly reduced ambient temperature (15–18 °C) and compared them with cold-exposed and room-temperature vehicle controls using systematic neurobehavioral testing. Despite the deep hypothermia (and the hypometabolism documented for this model), Y-maze spontaneous alternation performance was unaffected. Locomotor activity fell transiently during post-arousal recovery, with concurrent increases in self-directed behaviors. These results support further evaluation of this reversible metabolic intervention for critical care medicine and future human space missions.