title: Valproic acid inhibits excess dopamine release in response to a fear-conditioned stimulus in the basolateral complex of the amygdala of methamphetamine-sensitized rats.
abstract: 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.
authors.affiliation: Department of Psychiatry, Tokyo Women׳s Medical University, 8-1, Kawada-Cho, Shinjuku-Ku, Tokyo 168-8666, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Miyagi
authors.affiliation: Department of Psychiatry, Tokyo Women׳s Medical University, 8-1, Kawada-Cho, Shinjuku-Ku, Tokyo 168-8666, Japan. Electronic address: hidehiro.oshibuchi@gmail.com.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Oshibuchi
authors.affiliation: Department of Psychiatry, Tokyo Women׳s Medical University, 8-1, Kawada-Cho, Shinjuku-Ku, Tokyo 168-8666, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kasai
authors.affiliation: Department of Psychiatry, Tokyo Women׳s Medical University, 8-1, Kawada-Cho, Shinjuku-Ku, Tokyo 168-8666, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Inada
authors.affiliation: Department of Psychiatry, Tokyo Women׳s Medical University, 8-1, Kawada-Cho, Shinjuku-Ku, Tokyo 168-8666, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ishigooka
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D005239:Fear / Q000187:drug effects / Q000523:psychology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D008694:Methamphetamine; D014635:Valproic Acid; D004298:Dopamine
keywords: Amygdala; Dopamine; Fear conditioning; In vivo microdialysis; Methamphetamine sensitization; Valproic acid