title: Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism.
abstract: In the forced swim test (FST) rodents progressively show increased episodes of immobility if immersed in a beaker with water from where escape is not possible. In this test, a compound qualifies as a potential antidepressant if it prevents or delays the transition to this passive (energy conserving) behavioural style. In the past decade however the switch from active to passive "coping" was used increasingly to describe the phenotype of an animal that has been exposed to a stressful history and/or genetic modification. A PubMed analysis revealed that in a rapidly increasing number of papers (currently more than 2,000) stress-related immobility in the FST is labeled as a depression-like phenotype. In this contribution we will examine the different phases of information processing during coping with the forced swim stressor. For this purpose we focus on the action of corticosterone that is mediated by the closely related mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in the limbic brain. The evidence available suggests a model in which we propose that the limbic MR-mediated response selection operates in complementary fashion with dopaminergic accumbens/prefrontal executive functions to regulate the transition between active and passive coping styles. Upon rescue from the beaker the preferred, mostly passive, coping style is stored in the memory via a GR-dependent action in the hippocampal dentate gyrus. It is concluded that the rodent's behavioural response to a forced swim stressor does not reflect depression. Rather the forced swim experience provides a unique paradigm to investigate the mechanistic underpinning of stress coping and adaptation.
authors.affiliation: Division of Medical Pharmacology and Leiden Academic Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, Netherlands; Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
authors.forename: E R
authors.initials: ER
authors.lastname: de Kloet
authors.affiliation: Institute of Psychology, Leiden University, Wassenaarseweg 52, 2333 AK Leiden, Netherlands; Leiden Institute for Brain and Cognition, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Molendijk
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D005938:Glucocorticoids / Q000502:physiology; D008032:Limbic System / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D013550:Swimming
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid