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Behavioral Pharmacology

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Methylphenidate improves ADHD-like behavior only in adult DAT KO mice but not in juveniles

  • P3-352
  • 久保 有美子 / Yumiko Kubo:1,2 笠原 好之 / Yoshiyuki Kasahara:1,2 富田 博秋 / Hiroaki Tomita:1,2 有銘 預世布 / Yosefu Arime:2 高松 幸雄 / Yukio Takamatsu:3 池田 和隆 / Kazutaka Ikeda:3 曽良 一郎 / Ichiro Sora:2,4 
  • 1:東北大院医災害精神医学 / Dept. of Disaster Psychiatry, IRIDeS, Miyagi, Japan 2:東北大院医精神・神経生物 / Dept. of Biol Psychiatry, Tohoku Univ Grad. Sch. of Med., Miyagi, Japan 3:東京都医学総合研依存性薬物プロジェクト / Res. Project for Addictive Substances, Tokyo Metropolitan Inst. of Med Sci., Tokyo, Japan 4:神戸大院医精神医学 / Dept. of Psychiatry, Kobe Univ Grad. Sch. of Med. Hyogo, Japan 

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous syndrome manifesting symptoms including hyperactivity, impulsivity and inattention. The incidence of these symptoms typically changes with age, and often persists into adulthood. Dopamine transporter (DAT) knockout (KO) mice exhibit remarkable hyperactivity, and therefore have been widely considered as an animal model of ADHD. Although developmental process may be involved in the pathogenesis of ADHD, there have been few studies to evaluate developmental process of this mouse model. We have thus tested and compared locomotor activities of 4 weeks vs 12 to 20 weeks old DAT KO and wildtype (WT) littermate mice in a novel environment with or without methylphenidate (a non-selective dopamine/norepinephrine transporter inhibitor) pretreatment, as well as nisoxetine (a selective norepinephrine transporter inhibitor), or guanfacine (a selective α2A-adrenergic receptor agonist). Unpretreated DAT KO mice displayed greater locomotion than WT littermates regardless of age. Methylphenidate (3, 10, 30, or 60 mg/kg) significantly reduced hyperactivity in 12 to 20 weeks old DAT KO mice, whereas the same dose of methylphenidate failed to reduce locomotion in 4 weeks old DAT KO mice. Conversely, effects of methylphenidate did not differ in younger vs older WT mice. On the other hand, both nisoxetine (10, 30, 60 mg/kg) and guanfacine (0.1, 0.3, 1.0 mg/kg) pretreatments decreased hyperactivity both in 4 weeks and 12 to 20 weeks old DAT KO mice to approximately the same extent, compared to each WT littermate control. This study revealed for the first time that DAT KO mice display age-dependent differences in response to ADHD therapeutics, and indicated a possibility of different pharmacological effects, which may be relevant to the noradrenergic systems, of the therapeutic drugs through brain development.

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