Antidepressant mechanisms of venlafaxine involving increasing histone acetylation and modulating tyrosine hydroxylase and tryptophan hydroxylase expression in hippocampus of depressive rats. Issue 4 (6th March 2019)

• Record Type: Journal Article
• Authors: Qiao, Min; Jiang, Qing-Song; Liu, Ying-Ju; Hu, Xiao-Ya; Wang, Li-Jia; Zhou, Qi-Xin; Qiu, Hong-Mei
• Is Part Of: NeuroReport. Volume 30:Issue 4(2019)
• Publication Date: 2019-03-06
• Subjects: depression -- histone lysine residues catalyzed by histone deacetylases -- histone acetylation -- tyrosine hydroxylase -- tryptophan hydroxylase -- venlafaxine; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000001191
• Languages: English
• ISSNs: 0959-4965

Abstract

Abstract : Venlafaxine (VEN) is a widely used antidepressant as a serotonin-reuptake and norepinephrine-reuptake inhibitor. It is used primarily in depression, especially with generalized anxiety disorder or chronic pain. This medicine is of interest because its mechanisms involved multiple aspects. In the current study, the antidepressant action of VEN was investigated by studying the histone acetylation and expression of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) in rats exposed to chronic unpredicted stress (CUS) for 28 days. Male Sprague-Dawley rats were divided into a control group, VEN-treated control group, CUS group, and VEN-treated CUS group. VEN (23.4 mg/kg once daily) was administered to rats by intragastric gavage, whereas the same volume of vehicle was given to rats in the control and model groups. Rat behaviors, acetylated H3 at lysine 9 (acH3K9), acetylated H3 at lysine 14 (acH3K14), acetylated H4 at lysine 12 (acH4K12), histone deacetylase 5, and TH and TPH expression in the hippocampus were determined. Chronic VEN treatment significantly relieved the anxiety- and depression-like behaviors, prevented the increase of histone deacetylase 5 expression and decrease of acH3K9 level, and promoted TH and TPH protein expression in the hippocampus of CUS rats. The results suggest that the preventive antidepressant mechanism of VEN is partly involved in the blocking effects on histone de-acetylated modification and then increasing TH, TPH expression.