title: Dynamic changes in AP-1 transcription factor DNA binding activity in rat brain following administration of antidepressant amitriptyline and brain-derived neurotrophic factor.
abstract: The present study was undertaken to examine the effects of the antidepressant, amitriptyline, and brain-derived neurotrophic factor (BDNF) on activator protein-1 (AP-1) DNA binding activity in the rat brain. Acute administration of amitriptyline (5 or 10 mg/kg) initially increased but then decreased AP-1 DNA binding activity in the rat frontal cortex and hippocampus. Chronic administration of amitriptyline (5 or 10 mg/kg, once daily for 3 weeks) initially decreased AP-1 DNA binding activity but ultimately resulted in its persistent elevation in the rat frontal cortex. In contrast, the chronic administration of amitriptyline did not affect the low activity of AP-1 DNA binding in the hippocampus. However, chronic administration of amitriptyline (10 mg/kg, once daily for 3 weeks) significantly increased BDNF protein levels in the hippocampus (by 26.9%) and frontal cortex (by 24.6%). Direct infusion of BDNF (1 microg) into the hippocampal dentate gyrus significantly increased hippocampal AP-1 DNA binding activity. These results suggest that AP-1 transcription factor may be modulated by BDNF and that it may be an important target for the action of antidepressants.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba 260-8677, Japan. okamo@med.teikyo-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Shino
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: C
authors.initials: C
authors.lastname: Kumakiri
authors.forename: E
authors.initials: E
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Shirasawa
authors.forename: M
authors.initials: M
authors.lastname: Iyo
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; D018808:Transcription Factor AP-1; D000639:Amitriptyline; D004247:DNA