Too Depressed to Swim or Too Afraid to Stop? A Reinterpretation of the Forced Swim Test as a Measure of Anxiety-Like Behavior.

Abstract

Depression is one of the most common forms of mental illness. Despite decades of research, the mechanisms underlying this disorder remain unknown. To help elucidate the pathophysiology of depression, researchers are developing animal models of psychiatric disorders, including depression, and assessing for mood-related phenotypes. There are a limited number of behavioral assays available to assess depression-like behaviors in rodents but by far the most common is the forced swim test (FST). Although the FST is considered the gold standard for studying depression-like behaviors, there are strong reasons to question the interpretation that immobility represents ‘despair’ and escape-directed behaviors such as climbing represent the absence of a depression-like phenotype. It has recently been proposed that immobility in the FST is an adaptive learned response and reflects a switch from active to passive coping strategies (De Kloet and Molendijk, 2016). Although we agree with De Kloet and Molendijk (2016) that immobility is adaptive, we disagree on the interpretation of active versus passive coping strategies. Instead, we believe that escape-directed behaviors are driven by anxiety. We argue this perspective on the basis of comorbidity, gene targeting, and pharmacological studies.