Distinct effects of chronic antidepressant treatment on anxiety and depression-related behavior and stress hormone system regulation in an inbred mouse model for affective disorders

Dysregulations of the hypothalamic-pituitary-adrenocortical (HPA) system critically contribute to the pathogenesis of anxiety disorders and depression. Antidepressant drugs, in turn, restore homeostasis of the stress hormone system by yet unknown mechanisms. Thus, we performed a refined analysis of effects of a chronic antidepressant treatment on neuroendocrine reactions and behavioral responses towards stress-related stimuli in behaviorally distinct inbred mouse strains (C57BL/A; DBA/2). Mice were treated with paroxetine (2*10mg/kg, po.) for 21 days and consecutively subjected to an elevated-plus maze test assessing anxiety and a forced swimming test as a depression-related test. We further used in vivo microdialysis to monitor intrahippocampal free corticosterone in response to a mild and a severe stressor under chronic paroxetine administration. We found, that paroxetine treatment reversed high anxiety-levels and a passive stress coping in DBA mice, no behavioral effects were detected in C57. With respect on intrahippocampal corticosterone levels, significant effects were only observed in C57. Further assessing the antidepressant's effects on HPA system regulation, we performed in situ hybridisation studies on MR and GR (hippocampus), CRF and AVP (PVN, Amygdala) and detected significant strain and treatment effects. Thus, we provide further evidence for distinct effects of antidepressants on behavior and, associated with this, the stress hormone system regulation.