3-P-049
ヒスタミンH3受容体逆作動薬は、マウスにおいてヒスタミンH1受容体を介して覚せい剤誘導過運動を減弱する
Histamine H3 receptor inverse agonists attenuate methamphetamine-induced hyperlocomotion in mice via histamine H1 receptors
〇北中 順惠1、北中 純一1、天津 優紀恵1、大澤 礼奈1、佐藤 実歩1、橋本 紘卓1、久富 衣璃菜1、喜多尾 衣莉1、三村 真梨1、中村 美裕1、田上 健太1、田中 康一2、富田 和男2,3、佐藤 友昭3、西山 信好2、竹村 基彦1
Nobue Kitanaka1, Junichi Kitanaka1, Tukie Amatsu1, Rena Ozawa1, Miho Sato1, Kotaku Hashimoto1, Erina Hisatomi1, Eri Kitao1, Mari Mimura1, Miyu Nakamura1, Kenta Tagami1, Koh-Ichi Tanaka2, Kazuo Tomita2,3, Tomoaki Sato3, Nobuyoshi Nishiyama2, Motohiko Takemura1
1兵庫医科大・医・薬理、2兵庫医療大・薬・薬理、3鹿児島大・院医歯学総合・歯科応用薬理
1Dept. Pharmacol., Hyogo Col. Med., 2Div. Pharmacol., Dept. Pharm., Sch. Pharm., Hyogo Univ. Hlth. Sci., 3Dept. Applied Pharmacol., Grad. Sch. Med. Dent. Sci., Kagoshima Univ.
A single administration with METH induced a hyperlocomotion in mice. Pretreatment of mice with pitolisant, a histamine H3 receptor inverse agonist, for 30 min showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle-pretreated subjects, in a dose-dependent manner. Pretreatment of mice with JNJ-10181457, another H3 receptor inverse agonist, showed a similar inhibitory effect on METH-induced hyperlocomotion. No significant change in locomotion was observed in mice pretreated with pitolisant or JNJ-10181457 alone. Pretreatment with pitolisant prior to a high-dose METH significantly decreased the intensity of stereotyped behaviors and increased its latency to onset in a dose-dependent manner. The pitolisant action on METH-induced hyperlocomotion was completely abolished by a H1 receptor antagonist pyrilamine, but not by H2 receptor antagonist zolantidine. These observations suggest that pretreatment with pitolisant attenuates METH-induced hyperlocomotion via histamine receptors subtype H1 but not H2, and support the idea that activation of brain histamine systems may be a good strategy for the development of agents which treat METH abuse.