Chronic stress-induced changes in the rat brain: Role of sex differences and effects of long-term tianeptine treatment

• Published in: Neuropharmacology Vol. 75; pp. 426 - 436
• Main Authors: Kuipers, Sjoukje D., Trentani, Andrea, van der Zee, Eddy A., den Boer, Johan A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2013
• Subjects: Adrenal Glands - pathology; Animals; Antidepressive Agents, Tricyclic - therapeutic use; Body Weight - drug effects; BrdU; Bromodeoxyuridine - metabolism; Chronic stress; Corticosterone - blood; CREB phosphorylation; CREB-Binding Protein - metabolism; Electroshock - adverse effects; Female; FOS expression; Hippocampus - drug effects; Hippocampus - physiopathology; Male; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Wistar; Sex differences; Sex Factors; Stress, Psychological - blood; Stress, Psychological - drug therapy; Stress, Psychological - etiology; Stress, Psychological - pathology; Thiazepines - therapeutic use; Thymus Gland - pathology; Tianeptine; Time Factors; FOS expression; Sex differences; Chronic stress; CREB phosphorylation; Tianeptine; BrdU
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2013.08.018

Growing evidence suggests neuroplasticity changes are pivotal in both the occurrence and treatment of affective disorders. Abnormal expression and/or phosphorylation of numerous plasticity-related proteins have been observed in depression, while prolonged antidepressant treatment has been associated with the attenuation of stress-mediated effects on dendritic remodeling and adult hippocampal neurogenesis in experimental animals. This study explores the neurobiological adaptations induced by chronic stress and/or long-term tianeptine treatment. Male and female rats were studied to determine the potential contributory role of sex differences on stress-induced pathology and antidepressant-mediated actions. Our results confirm chronic stress-induced HPA axis disturbance and neuroplasticity impairment in both sexes (i.e. reduced CREB phosphorylation and hippocampal BrdU labeling). Commonly ensuing neurobiological alterations were accompanied by unique sex-specific adaptations. When the antidepressant tianeptine was administered, HPA axis hyperactivity was attenuated and specific neuronal defects were ameliorated in both sexes. These findings provide novel insight into sex-related influences on the neurobiological substrates mediating chronic stress-induced actions on neuroplasticity and the mechanisms underlying tianeptine-mediated therapeutic effects. •Sex-related dimorphisms were identified on FOS immunoreactivity, CREB phosphorylation and HPA activation.•Chronic stress impaired neuroplasticity and HPA axis regulation in both sexes.•Tianeptine attenuated stress-induced impairments in a sex-specific manner.•Tianeptine modulated prefrontocortical activity in females and HPA axis activation in males.