BEHAVIORAL AND PHYSIOLOGICAL MARKERS OF EXPERIMENTAL DEPRESSION INDUCED BY SOCIAL CONFLICTS (DISC)

This paper summarizes data confirming the development of depression in duced by social conflicts (DISC) in male mice of C57BL/6J strain. Repe ated defeat experiences in daily agonistic confrontations induced dram atic changes in behaviors as well as in the somatic state of submissiv e mice (losers) that were similar to symptoms of human depression with respect to etiology, susceptibility to treatment, and symptomatology. A remarkable behavioral deficit was found in losers, who demonstrated only a passive defense and immobile postures after 20 daily defeats ( tests) instead of active defense and withdrawal, which had predominate d in the first confrontations. Losers never demonstrated any aggressio n to other individuals and displayed a decrease in ambulation in the o pen-field test as well as an increase in immobility time in Porsolt's test. The development of anxiety and disturbance in communicative beha vior were observed in losers. Loss of weight and enhancement of gastri c mucosa damage, as well as a decrease in plasma testosterone level an d immune resistance, were shown in losers. Chronic imipramine and tian eptine treatment prevented the increase of ''depressiveness'' as estim ated by Porsolt's test. Chronic unavoidable social stress is considere d a pathogenic factor, which leads to the development of depressive pa thology and anxiety in mice. The study on brain monoaminergic activity in losers at different stages of the experimental depression allows t he hypothesis that the development of depression is accompanied by dyn amic changes in turnover and reception of at least brain serotonin, de pending on the duration and depth of the pathological depressive proce sses. Behavioral and physiological markers of a depression-like state in losers are discussed in comparison with those of human depressive d isorder. (C) 1998 Wiley-Liss, Inc.