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Animals placed in a container filled with water show periods of increased swimming activity and periods of relative immobility. Clinically active anti-depressants have been found to delay the onset of the first phase of immobility and to reduce the total time of relative immobility. The list of active compounds includes monoamino-oxidase-A (MAO-A) inhibitors such as moclobemide, brofaromine, noradrenaline (NA) uptake inhibitors such as imipramine and amytryptilin, MAO-B inhibitors such as selegiline and tranylcypromine, serotonin uptake inhibitors (SSRI) such as fluoxetine and paroxetine and combined NA / SSRI such as venlafaxine. Benzodiazepines and other types of psychoactive compounds have been found to be inactive in this test.
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Porsolt RD, Bertin A, Jaffre M. Behavioral despair in rats and mice: strain differences and the effect of imipramine.