Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat

• Published in: Brain research Vol. 1366; pp. 141 - 148
• Main Authors: Zhang, Yang, Gu, Fenghua, Chen, Jia, Dong, Wenxin
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 17.12.2010; Elsevier
• Subjects: ACTH; Adrenocorticotropic Hormone - blood; Adult and adolescent clinical studies; Animals; Antidepressive Agents - pharmacology; BDNF; Biological and medical sciences; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; CORT; Corticosterone - blood; CUMS; Depression; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay - methods; Frontal Lobe - drug effects; Frontal Lobe - metabolism; Gene Expression Regulation - drug effects; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medical sciences; Mood disorders; Neurology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; RNA, Messenger - metabolism; Stress, Psychological - blood; Stress, Psychological - drug therapy; Stress, Psychological - pathology; ACTH; CORT; Depression; BDNF; CUMS; Mood disorder; Rat; Psychotropic; Rodentia; Central nervous system; Stress; Encephalon; Vertebrata; Chronic; Mammalia; Adrenocorticotropic hormone; Treatment; Adenohypophyseal hormone; Animal; Frontal; Antidepressant agent; Brain derived neurotrophic factor; Hippocampus
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2010.09.095

Abstract Stress activates the hypothalamo–pituitary–adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects.