The neuropeptides thyrotropin releasing hormone (TRH) and prolactin (PRL), which affect various behaviors in animals, showed "antidepressant" properties in an experimental model of depression. Subcutaneous administration of TRH reduced the total immobility time of rats tested in the despair (constrained swim) test and potentiated the anti-immobility effect of intraperitoneally administered desimipramine (DMI). This effect was not mimicked by the peripheral injection of TSH, T3 or T4. Hyperprolactinemia induced by pituitary homografts under the kidney capsule and the intracerebroventricular injection of PRL also potentiated the DMI-induced reduction of total immobility time of rats in the despair test and exerted "antidepressant" effects in aged rats.