Animal model of depression: tests of three structurally and pharmacologically novel antidepressant compounds

Previous studies have identified behavioral and neuroendocrine abnormalities in chronically stressed rats which resemble some of the more prominent features of clinical depression. These abnormalities have proved responsive to pharmacotherapy by standard antidepressant drugs and related somatic treatments. Several structurally and pharmacologically atypical compounds, resembling neither standard agents, nor each other, have recently been identified as clinically effective antidepressants. There drugs do not show typical preclinical response profiles in other drug screening tests and, therefore, represent critical instances for evaluating the selectivity of the chronic stress model. Three drugs were tested, these being iprindole, bupropion, and mianserine; a tricyclic indole, propriophenone, and tetracyclic compound respectively. Four circulating measures, which previously proved most useful in discriminating antidepressant potential, and a measure of circulating corticosterone were obtained for subjects examined factorially in a 2x2x2 experimental design (chronic stress vs none, acute stress vs none, and drugs vs control). All compounds proved capable of reversing chronic stress induced behavioral deficits, and all but one compound reversed the attendant basal hypersecretion of corticosterone. These findings argue that the chronic stress model provides an accurate and selective assessment of the therapeutic potential of both standard and structurally novel compounds.