Corticosteroid receptor immunoreactivity in neurons of the hippocampus, amygdala and paraventricular nucleus, in rats under maternal separation and chronic stress: Effects of tianeptine

Abstract

Hippocampus, amygdala and paraventricular nucleus of hypothalamus (PVN), which belong to the reward system, widely express Gluco- and mineralo- corticoid receptors (GR and MR, respectively) and are critically involved in the regulation of stress response. It has been well established that stress both during early life as well as in adulthood, increases the susceptibility of developing depression. The aim of this work was to determine the effect of chronic treatment with 10 mg/Kg of tianeptine on GR and MR expression in the layers CA1, CA2, CA3 and dentate gyrus (DG) of dorsal hippocampus, medial amygdala and PVN, in male Wistar rats submitted to early maternal separation and variable chronic stress as adults (a model of depression). GR and MR levels were determined by immunohistochemistry. In hippocampus and amygdala, we found that in non-maternally separated (NMS) groups, animals subjected to stress showed more GR immunoreactive (GR-ir) cells, whereas in maternally separated (NS) groups, stress decreased the number of these neurons, showing similar levels to control group (p<0,05). Furthermore, there was a similar effect in the MR immunoreactivity (MR-ir) (p<0,05) in the layers CA2 and DG of the hippocampus. Besides, in the layers CA1 and CA2, we found less GR-ir and MR-ir neurons in MS-stressed compared with NMS-stressed group (p<0,05). In MS-stressed animals, daily administration of the antidepressant tianeptine increased GR-ir in hippocampus and amygdala and MR-ir in DG of hippocampus and PVN (p<0,05). In conclusion, stressed animals show a differential regulation of GR and MR levels in dorsal hippocampus, PVN and medial amygdala, according with early life events. Whereas tianeptine increased GR-ir and MR-ir in MS-stressed animals, which might attenuate the upsetting of hypothalamic-pituitary-adrenal axis.