Thermoregulatory significance of immobility in the forced swim test

The forced swim test (FST) is a widely used animal model of depression and antidepressant drug screen. Rats are forced to swim on two test days in a restricted space from which there is no escape. On the first test day the rats attempt to escape and then become largely immobile; on the second test day the onset of immobility is more rapid. Immobility is said to reflect a state of lowered mood or behavioral despair, but the validity of the FST as a model of depression has been questioned. We show here that whatever psychological states the FST may induce, immobility is water temperature dependent and thermoregulatory. In Experiment 1, separate groups of rats were first tested in water of 15, 20, 22, 25, 30, 35, 37, or 40 degrees C. When retested at the same temperature, reduced activity was evident only in those groups tested above 20 degrees C and below 37 degrees C. On a third test, rats previously tested in 35 degrees C water failed to show reduced activity in 15 degrees C water, whereas rats previously tested at 15 degrees C water did exhibit reduced activity when tested in 35 degrees C water. Thus, activity was dependent on current water temperature rather than prior experience. In Experiment 2, activity and body temperature were monitored during 30 min swim tests in 27 degrees C water. The more the animals moved, the greater the loss of body temperature. The results are consistent with a hypothesis that immobility in the FST is an adaptive thermoregulatory response that increases survival by minimizing convective heat loss. This interpretation is also aligned with best practices for survival of humans in water that is below thermoneutral.

Automated summary

The forced swim test (FST) is a widely used animal model for studying depression and screening antidepressant drugs. However, the validity of FST as a model of depression has been questioned. This study shows that immobility in the FST is temperature-dependent and related to thermoregulation. The results suggest that immobility is an adaptive response to minimize heat loss and increase survival. These findings imply that FST may not accurately reflect depressive behavior but rather a thermoregulatory strategy.