Learned helplessness: Validity and reliability of depressive-like states in mice

• Published in: Brain research. Brain research protocols 2005-12, Vol.16 (1), p.70-78
• Main Authors: Chourbaji, S., Zacher, C., Sanchis-Segura, C., Dormann, C., Vollmayr, B., Gass, P.
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - pharmacology; Antidepressive treatment; Avoidance Learning - drug effects; Avoidance Learning - physiology; Depressive Disorder - psychology; Depressive-like behavior; Electroshock; Helplessness, Learned; Imipramine - pharmacology; Learned helplessness; Male; Mice; Mice, Inbred C57BL; Pain Measurement - drug effects; Reaction Time - drug effects; Reaction Time - physiology; Reproducibility of Results
• ISSN: 1385-299X
• DOI: 10.1016/j.brainresprot.2005.09.002

The learned helplessness paradigm is a depression model in which animals are exposed to unpredictable and uncontrollable stress, e.g. electroshocks, and subsequently develop coping deficits for aversive but escapable situations (J.B. Overmier, M.E. Seligman, Effects of inescapable shock upon subsequent escape and avoidance responding, J. Comp. Physiol. Psychol. 63 (1967) 28–33 [15]). It represents a model with good similarity to the symptoms of depression, construct, and predictive validity in rats. Despite an increased need to investigate emotional, in particular depression-like behaviors in transgenic mice, so far only a few studies have been published using the learned helplessness paradigm. One reason may be the fact that—in contrast to rats (B. Vollmayr, F.A. Henn, Learned helplessness in the rat: improvements in validity and reliability, Brain Res. Brain Res. Protoc. 8 (2001) 1–7)—there is no generally accepted learned helplessness protocol available for mice. This prompted us to develop a reliable helplessness procedure in C57BL/6N mice, to exclude possible artifacts, and to establish a protocol, which yields a consistent fraction of helpless mice following the shock exposure. Furthermore, we validated this protocol pharmacologically using the tricyclic antidepressant imipramine. Here, we present a mouse model with good face and predictive validity that can be used for transgenic, behavioral, and pharmacological studies.