日本毒性学会学術年会
第47回日本毒性学会学術年会
セッションID: P-104
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有機リン系化合物曝露後の内因性カンナビノイド系を介した幼若ラットのADHD 様行動
*伊藤 由起冨澤 元博鈴木 和貴白川 雄一大野 弘眞足立 圭司鈴木 日美子下村 健司鍋島 俊隆上島 通浩
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Anticholinergic organophosphate (OP) agents act on the diverse serine hydrolases, thereby revealing unexpected biological effects. Epidemiological studies indicate a relationship between OP exposure and development of attention-deficit/hyperactivity disorder (ADHD)-like symptoms, whereas no plausible mechanism for the OP-induced ADHD has been established. The present investigation employs EOPF as an OP-probe which is an extremely potent inhibitor of endocannabinoid (EC, anandamide and 2-arachidonoylglycerol)-hydrolyzing enzymes: i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Ex vivo experiment shows that EOPF treatment decreases FAAH and MAGL activities and conversely increases EC levels in rat brain. Subsequently, EOPF (treated intraperitoneally once at 0, 1, 2, or 3 mg/kg) clearly induces ADHD-like behaviors (in elevated plus-maze test) in both Wistar and spontaneously hypertensive rats. The EOPF-induced behaviors are reduced by a concomitant administration of cannabinoid receptor inverse agonist SLV-319. Accordingly, EC system is a feasible target for OP-caused ADHD-like behaviors in adolescent rats.

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