Induced depressive behavior impairs learning and memory in rats.

While it is generally accepted that cognitive processes such as learning and memory are affected by emotion, the impact of depression on learning and memory has rarely been directly studied in experimental animals. Effects of induced depressive behavior on learning and memory were determined in rats, using an open space swim test, a novel animal model of depressive behavior that is developed recently in our laboratory. The model indexes searching activity of the animals, with the induced depressive immobility behavior showing specific sensitivity to three major prototypic classes of antidepressants and a selective serotonin reuptake inhibitor. The induced depressive behavior in rats showed a delayed response to chronic antidepressant treatment and had a lasting effect on the ability of rats to learn and recall the learned experience. It impaired the subsequent ability of rats to learn and recall both a spatial water maze task and a multi-trial passive avoidance task. These impairments were all sensitive to antidepressant therapeutics, but not to buspirone, an anxiolytic. By way of contrast, the ability of the rats to sense and move to a visible platform and to escape from an unconditioned shock stimulus was neither impaired by inducing the depressive behavior nor altered by the drug treatment, suggesting that non-specific changes in sensorimotor ability were not involved. These impairments of learning and memory indicate that the depressive behavior-induced deficits show generalizability and are not context-limited. This animal model of depressive behavior shows promising potential as a screen for novel antidepressive therapeutics and as a disease model for revealing network/cellular/molecular mechanisms in the pathophysiology of depression and depression-induced cognitive deficits.