Animal Models of Depression - Chronic Despair Model (CDM)

Vestring, Stefan; Serchov, Tsvetan; Normann, Claus

doi:10.3791/62579-v

JoVE

2021

DOI: 10.3791/62579-v

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Animal Models of Depression - Chronic Despair Model (CDM)

Stefan Vestring

Tsvetan Serchov

Claus Normann

Abstract: The chronic despair mouse model (CDM) of depression consists of repetitive forced swim sessions and another delayed swim phase as a read-out. It represents a suitable model for induction of a chronic depressive-like state stable for at least 4 weeks, amendable to evaluate subchronic and acute treatment interventions.

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Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice

Sarrazin,

Gardner,

Marchese

et al. 2024

Nat Commun

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Depression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant ketamine. Selective Bmal1KO in CaMK2a excitatory neurons revealed that the functional mPFC clock is an essential factor for the development of a depression-like phenotype and ketamine effects. Per2 silencing in mPFC produced antidepressant-like effects, while REV-ERB agonism enhanced the depression-like phenotype and suppressed ketamine action. Pharmacological potentiation of clock positive modulator ROR elicited antidepressant-like effects, upregulating plasticity protein Homer1a, synaptic AMPA receptors expression and plasticity-related slow wave activity specifically in the mPFC. Our data demonstrate a critical role for mPFC molecular clock in regulating depression-like behavior and the therapeutic potential of clock pharmacological manipulations influencing glutamatergic-dependent plasticity.

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Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice

Sarrazin,

Gardner,

Marchese

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

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Animal Models of Depression - Chronic Despair Model (CDM)

Cited by 1 publication

References 14 publications

Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice

Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice

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