ノルアドレナリントランスポーターの阻害により、内側前頭前野腹側部のドパミンD1様受容体が刺激され、衝動性の制御機能が向上する

• Published in: 日本薬理学会年会要旨集 p. 2-O-16
• Main Authors: 笹森, 瞳, 吉岡, 充弘, 大村, 優
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2019
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.92.0_2-O-16

Higher impulsivity is a risk factor for substance abuse and suicide, but only a few anti-impulsive drugs are clinically available. We recently proposed a strategy for identifying anti-impulsive drugs by investigating drugs that increase extracellular dopamine levels in the medial prefrontal cortex (mPFC) and stimulate dopamine D1-like receptors, but not in the nucleus accumbens (NAc). To determine whether this strategy is promising, we examined the effects of duloxetine, a serotonin-noradrenaline reuptake inhibitor that might meet these criteria, on impulsive action in adult male Wistar/ST rats using a 3-choice serial reaction time task. The effects of duloxetine on the dopamine levels in the areas were evaluated using in vivo microdialysis, as the noradrenaline transporter mediates dopamine reuptake in some brain regions. We found that the administration of duloxetine reduced impulsive actions and increased dopamine levels in the mPFC but not in the NAc. Microinjection of a D1-like receptor antagonist into the ventromedial prefrontal cortex blocked the suppression of impulsive action by duloxetine. These results support our proposed strategy for identifying and developing anti-impulsive drugs.