- Intermittent hypoxia (IH), such as occurs in sleep apnea, is associated with increased apoptosis and neurobehavioral impairments in rats. To determine whether pre-training (P) modifies the effect of IH on spatial learning, adult male rats were trained in a spatial version of the water maze, exposed to IH or room air (RA) for 14 days, and then trained in a novel spatial task. P-RA had lower initial pathlengths than naive RA (N-RA), which were similar in P-IH and N-IH, indicating an adverse effect of IH on retention of behavioral strategies to solve the maze. However, P-IH acquired the later spatial task faster than N-IH. Pre-training was associated with increased phosphorylation of the cAMP-response element binding protein (CREB) in the hippocampus. Further, IH-induced decreases in CREB phosphorylation were attenuated by pre-training. We conclude that prior exposure to the water maze behavioral requirements attenuates the behavioral deficits occurring after IH exposure.