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PLoS One. 2015 Apr 30;10(4):e0125892. doi: 10.1371/journal.pone.0125892. eCollection 2015.

Dissociation of learned helplessness and fear conditioning in mice: a mouse model of depression.

Author information

1
Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America; Department of Psychiatry & Center for Circadian Biology, University of California San Diego, La Jolla, CA, United States of America.
2
Department of Psychiatry, University of California San Diego, La Jolla, CA, United States of America.
3
Animal Phenotyping Core, University of California San Diego, La Jolla, CA, United States of America.

Abstract

The state of being helpless is regarded as a central aspect of depression, and therefore the learned helplessness paradigm in rodents is commonly used as an animal model of depression. The term 'learned helplessness' refers to a deficit in escaping from an aversive situation after an animal is exposed to uncontrollable stress specifically, with a control/comparison group having been exposed to an equivalent amount of controllable stress. A key feature of learned helplessness is the transferability of helplessness to different situations, a phenomenon called 'trans-situationality'. However, most studies in mice use learned helplessness protocols in which training and testing occur in the same environment and with the same type of stressor. Consequently, failures to escape may reflect conditioned fear of a particular environment, not a general change of the helpless state of an animal. For mice, there is no established learned helplessness protocol that includes the trans-situationality feature. Here we describe a simple and reliable learned helplessness protocol for mice, in which training and testing are carried out in different environments and with different types of stressors. We show that with our protocol approximately 50% of mice develop learned helplessness that is not attributable to fear conditioning.

PMID:
25928892
PMCID:
PMC4416012
DOI:
10.1371/journal.pone.0125892
[Indexed for MEDLINE]
Free PMC Article

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