Behavioral and physiological markers of experimental depression induced by social conflicts (DISC)

Anhedonia in the Shadow of Chronic Social Defeat Stress, or when the Experimental Context Matters

“…We have demonstrated earlier that С57BL/6J strain male mice exposed to or affected by chronic social defeat stress develop a mixed anxiety/depression state or anxious depression, many symptoms of which are similar to those in depressive patients [29][30][31]. Knowing in advance that the mice were depressed, we examined their sucrose consumption in the twobottle free-choice paradigm, in various experimental situations [32][33][34] that in our opinion could account for the variability of results obtained using other depression models.…”

“…As has been earlier shown [reviews, [29][30][31]37], social defeat repeatedly experienced in agonistic interactions leads to dramatic changes in social and individual behaviors, as well as welfare. The losers developed a severe behavioral deficit: after experiencing social defeat for 20 days, they could only demonstrate a passive defense and immobile postures, whilst in the beginning they preferred active defense and withdrawal.…”

“…Chronic ethanol consumption [40] and chronic treatment with ipsapirone [41] reduced anxiety, but did not prevent depression. Chronic unavoidable social stress is believed to be a pathogenic factor that leads to a mixed anxiety/depression state in mice [30]. Changes in brain serotonergic activity were detected in mice losing fights [review, 31].…”

Reduction of serotonergic gene expression in the raphe nuclei of the midbrain under positive fighting experience in male mice

“…Thus, different mechanisms of brain serotonergic hypofunction can be assumed in the mice with alternative social behaviors. In the losers, strong decrease of serotonergic activity may be attributed to the development of a depressionlike condition with the symptoms, sensitivity to antidepressants and neurochemical changes similar to those in depressive patients [36,45,46]. In the winners behavioral psychopathology developing under positive fighting experience [15] is associated with inhibition of brain serotonergic system.…”

“…Similarity of changes in male mice with alternative social behaviors, manifested by chronic defeats or aggression casts doubt on the specificity of such changes for aggression. Earlier we assumed [44] that similar changes in the winners and losers may be explained by influence of agonistic interactions stress common for both participants of social conflicts or by development of enhanced level of anxiety shown both in the winners [24] and losers [45]. However we should also take into consideration the different dynamics of gene expression changes during period without agonistic interactions.…”