抗酒癖剤ジスルフィラムはマウスにおいて抗不安様作用を示す

• Published in: 日本薬理学会年会要旨集 p. 2-P1-32
• Main Authors: 長山, 佳史, 山田, 大輔, 寺島, 裕也, 牧野, 宏章, 髙橋, 美乃, 佐野, 良威, 遠田, 悦子, 大橋, 美咲, 吉岡, 寿倫, 岡野, 功太郎, 小俣, 知貴, 高橋, 秀依, 松島, 綱治, 斎藤, 顕宜
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: amygdala; anxiolytic; benzodiazepine; monoamine
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_2-P1-32

Recent study has demonstrated that anti-alcoholism drug disulfiram (DSF) inhibits chemokine receptor-mediated migration signals. Several studies have reported that the chemokine receptors are associated with emotion regulation. Therefore, this study was performed to clarify the effect of DSF on emotional behavior in rodents.Male ICR mice were used. In the elevated plus-maze test, a screening model for anxiolytics, DSF (40 mg/kg, i.p.) significantly produced the increases in the percentage of time spent on the open-arms without any effects on the total open arms entries. These behavioral changes were similar to that observed for the benzodiazepine anxiolytics diazepam (1.5 mg/kg, s.c.). In contrast to diazepam, DSF produced no effects on the spontaneous locomotor activity in mice. On the other hand, in the rotarod test, diazepam significantly increased the number of falls, suggesting the coordination disorder, whereas DSF produced no effects. Furthermore, DSF decreased noradrenaline content and increased dopamine content in mice amygdala.This is the first report suggesting that DSF produced the anxiolytic-like effects in rodents. We proposed that DSF could be an effective novel anxiolytic drug without the coordination disorder found in diazepam, and that the monoamine content changes in amygdala may be involved in its underlying mechanism.