Animal Models for Depression and the Mode of Action of Neurotransmitter Transporter-Blocking Antidepressants
Major depressive disorder is a highly prevalent and devastating mental illness whose underlying pathomechanisms remain incompletely understood. Currently the most commonly used antidepressants block neurotransmitter transporters, i.e., the transporters for serotonin (SERT) and/or norepinephrine (NET); in addition, there are compounds which regulate transmitter release by targeting presynaptic autoreceptors for norepinephrine and serotonin. There is an unmet medical need, because some patients respond poorly to the existing treatments. Preclinical models are required to test potential new antidepressant compounds. These models must recapitulate at least some of the symptoms of depression in animals and allow for the quantification of treatment effects on depression-like behavior. Here we present the chronic mild stress model as a suitable paradigm for eliciting depression-like behavior in mice. We describe the procedures used to interrogate the model by quantifying the induced behavioral phenotype, the associated physiological alterations and their modulation by drug candidates.
Key wordsAnimal model Behavior Depression Neurotransmitter transporter Anhedonia
The authors wish to thank the Austrian Science Fund for continuous support (grant F35).
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