title: Antidepressants and mood stabilizers effects on histone deacetylase expression in C57BL/6 mice: Brain region specific changes.
abstract: To determine whether treatment with various antidepressants or mood stabilizers leads to region-specific changes, we investigated the effects of their subchronic (14 days of intraperitoneal injection) administration on the tissue concentration of monoamines, dopamine, serotonin, and norepinephrine, and the protein expression of acetylated histone H3 (AcH3) and histone deacetylases (HDACs) in the mouse striatum (ST), nucleus accumbens (Acb), hippocampus (Hip), cingulate cortex (Cg), and amygdala (Amy). Subchronic administration with the antidepressants (S)-citalopram oxalate (ECM), duloxetine hydrochloride (DLX), and mirtazapine (MIR) commonly induced significant increases in dopamine and serotonin levels in the ST and Cg. By contrast, no common profiles for dopamine, serotonin, or norepinephrine were identified in the Acb, Hip, or Amy. Treatment with sodium valproate (VPA), lithium chloride (Li), lamotrigine (LTG), levetiracetam (LTM), olanzapine (OLZ), clozapine (CLZ), clomipramine (CLM), ECM, and DLX induced significant increases in AcH3 expression in the Acb, while treatment with CLM, ECM, DLX, MIR, carbamazepine (CBZ), LTG, LTM, OLZ, or CLZ induced significant increases in HDAC2 and HDAC3 in the ST. CLM, MIR, VPA, CBZ, LTG, LTM, OLZ, or CLZ induced significant increases in HDAC3 in the Cg, and ECM, DLX, MIR, VPA, CBZ, LTG, LTM, or OLZ resulted in significant increases in HDAC5 in the Amy. Collectively, the changes of monoamine content were restricted for mood stabilizer effects, but increased expression of HDAC2, HDAC3, or HDAC5 in the ST, Cg, or Amy was often found, supporting the possibility that antidepressant-like effects involve epigenetic modifications associated with changes in HDAC expression.
authors.affiliation: Department of Psychiatry, Shiga University of Medical Science, Japan; Department of Psychiatry, Minakuchi Hospital, Koka City, Japan. mookubo@belle.shiga-med.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Ookubo
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Kanai
authors.forename: Harusuke
authors.initials: H
authors.lastname: Aoki
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D015306:Biogenic Monoamines; D006655:Histone Deacetylases
keywords: Acetylated histone H3; Amygdala; Cingulate cortex; Depression; Histone deacetylases; Striatum