Intermittent hypoxia impairs performance of adult mice in the two‐way shuttle box but not in the Morris water maze

Abstract

We have previously found that neonatal intermittent hypobaric hypoxia exposure enhanced mouse spatial, but impaired associative, cognition. This study sought to investigate the effects of hypobaric hypoxia on adult mice cognition. Mice were exposed to 2, 5, 10, 15, or 25 days of intermittent hypoxia (IH; 4 hr/day) at 2 km (16.0% O₂) or 5 km (10.8% O₂) altitudes in a hypobaric chamber for the Morris water maze (MWM) test and exposed to IH for 2, 10, or 25 days for the shuttle‐box test. Amino acid dynamics in vivo in the hippocampus and amygdala of mice exposed to 2 km hypoxia were analyzed by high‐pressure liquid chromatography. The results in MWM task showed that IH‐2d to ‐25d at 2 km or 5 km did not change the escape latencies of mice in the training test or the retention of platform in the probe test. In the shuttle‐box task, however, IH‐10d at 5 km significantly reduced mouse avoidances in the acquisition test on day 4, and IH‐10d at 2 km reduced avoidances in the retention test; IH‐25d at 5 km significantly reduced avoidances of mice throughout the acquisition days. Glutamate in the amygdala persisted in declining to 69% of baseline at 8 hr posthypoxia (P = 0.040 vs. GLU released during 30 min before hypoxia) during the posthypoxia stage. These results suggest that adult hypobaric IH impairs the hippocampal‐independent, but not the hippocampal‐dependent, task in mice. The different GLU releases in the hippocampus and amygdala in response to hypoxia are involved in the different behaviors.