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An animal model of a behavioral intervention for depression.


ABSTRACT: Although conditioned inhibition of fear (or learned safety) is a learning process critical for preventing chronic stress, a predisposing factor for depression and other psychopathologies, little is known about its functional purposes or molecular mechanisms. To obtain better insight into learned safety, we investigated its behavioral and molecular characteristics and found that it acts as a behavioral antidepressant in two animal models. Learned safety promotes the survival of newborn cells in the dentate gyrus of the hippocampus, while its antidepressant effect is abolished in mice with ablated hippocampal neurogenesis. Learned safety also increases the expression of BDNF in the hippocampus and leads to downregulation of genes involved in the dopaminergic and neuropeptidergic but not the serotonergic system in the basolateral amygdala. These data suggest that learned safety is an animal model of a behavioral antidepressant that shares some neuronal hallmarks of pharmacological antidepressants but is mediated by different molecular pathways.

SUBMITTER: Pollak DD 

PROVIDER: S-EPMC3417703 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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An animal model of a behavioral intervention for depression.

Pollak Daniela D DD   Monje Francisco J FJ   Zuckerman Lee L   Denny Christine A CA   Drew Michael R MR   Kandel Eric R ER  

Neuron 20081001 1


Although conditioned inhibition of fear (or learned safety) is a learning process critical for preventing chronic stress, a predisposing factor for depression and other psychopathologies, little is known about its functional purposes or molecular mechanisms. To obtain better insight into learned safety, we investigated its behavioral and molecular characteristics and found that it acts as a behavioral antidepressant in two animal models. Learned safety promotes the survival of newborn cells in t  ...[more]

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