Profound hypothermia determines the anticonvulsant and neuroprotective effects of swim stress.

In contrast to most stressors that appear to be proconvulsant in nature, forced swimming (or swim stress) produces substantial anticonvulsant effects. Here we describe a series of experiments designed to identify the specific factors of swim stress (e.g., duration, swimming behavior, water temperature, and frequency of exposure) that are essential for the emergence of anticonvulsant effects in the rat. Our results revealed that the anticonvulsant effect of swim stress against lithium-pilocarpine convulsions occurred only when swim durations were at least 5 min in length and in water temperatures of 20 degrees C or less. Moreover, this anticonvulsant effect was not associated with habituation even after 10 days of repeated swimming. Treatment with lithium-pilocarpine coupled with 10 degrees C or 20 degrees C swim stress for 10 min caused pronounced hypothermia (10 to 15 degrees C reduction in body temperature) that required at least 12 h to return to baseline. One day after seizures were induced, swim stressed rats showed significantly fewer degenerating neurons in the hippocampus as revealed by Fluoro-Jade B staining. These results suggest that dramatically lowered body temperature could be the critical factor that produces the anticonvulsive and neuroprotective effects of swim stress.