Lasting effects of chronic social stress in mice: Impact of antidepressant treatment

Chronic stress represents a risk factor for a variety of human disorders. Although an increase in susceptibility to disease has clearly been shown, the molecular mechanisms of these effects remain elusive. We aimed at investigating the effects of antidepressant intervention on stress-induced aversive effects and its interplay with aging. Male CD1 mice were subjected to 7 weeks of chronic social stress during adolescence. Following the stress procedure, animals were treated with paroxetine for 4 weeks. Chronic social stress caused elevated basal corticosterone levels, accompanied by enlarged adrenal glands and involution of the thymus gland, 5 weeks after stress. In addition, habituation to a novel environment was impaired in stressed animals. Stress-induced alterations in hippocampal gene expression were analyzed using microarray technology. In the second part of the study, the animals were tested again 12 months after stress exposure. Stress during the adolescence caused alterations in stress responsivity. Paroxetine treatment was able to reverse the majority of stress-induced effects in the present study and exerted some long-term effects on stress-related parameters. Recapitulatory, chronic stress during the adolescence induced lasting differences in physiological, neuroendocrine and behavioural parameters as well as in gene expression 5 weeks and, to some degree, 12 months after stress. Most of these changes were reversible by paroxetine treatment.