The light-dark forced swim test for simultaneous assessment of behavioral ‘despair’ and anxiety-like behavior in female mice

Animal models are a valuable tool to study anxiety and depression, two common and severely debilitating brain disorders. Probing them experimentally typically relies on various rodent behavioral assays, such as the light-dark and the forced swim tests. However, the growing importance of testing novel CNS concepts and neuroactive drugs calls for further refinement of existing behavioral tests, as well as the development of new assays. One research strategy in this direction involves combining principles of several tests into one ‘hybrid’ assay. Using this approach, here we develop a novel ‘hybrid’ mouse assay, the light-dark forced swim test, combining features of the two conventional assays to simultaneously assess animal anxiety-like (light-dark preference during swimming) and depression-like behaviors (‘despair’-like immobility). Overall, the anxiety-like dark preference of female white outbred mice in this test is sensitive to physiological anxiogenic stressors (daily swimming or administration of prednisolone and dexamethasone), whereas clinically active antidepressants (fluoxetine and paroxetine) reduce despair-like immobility in this test. Collectively, these findings suggest that this novel assay may simultaneously evaluate anxiety- and depression-like behaviors, and can be applied to testing neuroactive drugs.