オシブチ　ヒデヒロ   OSHIBUCHI Hidehiro   押淵　英弘    所属   医学部 医学科（東京女子医科大学病院）    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Valproic acid inhibits excess dopamine release in response to a fear-conditioned stimulus in the basolateral complex of the amygdala of methamphetamine-sensitized rats.
掲載誌名	正式名：European journal of pharmacology 略　 称：Eur J Pharmacol ISSNコード：(1879-0712)0014-2999(Linking)
掲載区分	国外
巻・号・頁	730,pp.20-25
著者・共著者	Miyagi Junko, Oshibuchi Hidehiro, Kasai Akiko, Inada Ken, Ishigooka Jun
発行年月	2014/05
概要	Valproic acid, an established antiepileptic and antimanic drug, has recently emerged as a promising emotion-stabilizing agent for patients with psychosis. Although dopamine transmission in the amygdala plays a key role in emotional processing, there has been no direct evidence about how valproic acid acts on the dopaminergic system in the brain during emotional processing. In the present study, we tested the effect of valproic acid on a trait marker of vulnerability to emotional stress in psychosis, which is excess dopamine release in response to a fear-conditioned stimulus (CS) in the basolateral complex of the amygdala of methamphetamine-sensitized rats. Extracellular dopamine was collected from the amygdala of freely moving methamphetamine-sensitized rats by in vivo microdialysis and was measured using high-performance liquid chromatography. During microdialysis, valproic acid was intraperitoneally injected followed by CS exposure. Valproic acid treatment decreased baseline levels of dopamine and also attenuated the excess dopamine release in response to the CS in the amygdala of methamphetamine-sensitized rats. The results prove that valproic acid inhibits spontaneous dopamine release and also attenuates excess dopaminergic signaling in response to emotional stress in the amygdala. These findings suggest that the mechanisms of the emotion-stabilizing effect of valproic acid in psychosis involve modulation of dopaminergic transmission in emotional processing.
DOI	10.1016/j.ejphar.2014.01.020
PMID	24583338