PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice

被引：34

作者：

Brown, Jacquelyn A. ^{[1
]}

Xu, Jinbin ^{[2
]}

Diggs-Andrews, Kelly A. ^{[1
]}

Wozniak, David F. ^{[3
]}

Mach, Robert H. ^{[2
]}

Gutmann, David H. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

来源：

EXPERIMENTAL NEUROLOGY | 2011年 / 232卷 / 02期

关键词：

Dopamine; Behavior; Neurofibromin; Cyclic AMP; RAS; SELECTIVE RADIOLIGAND; DOPAMINE D-3; MOUSE MODEL; TYPE-1; BRAIN; METHYLPHENIDATE; HETEROZYGOSITY; UNDERLIES; DISORDER; CHILDREN;

D O I：

10.1016/j.expneurol.2011.09.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Attention system abnormalities represent a significant barrier to scholastic achievement in children with neurofibromatosis-1 (NF1). Using a novel mouse model of NF1-associated attention deficit (ADD), we demonstrate a presynaptic defect in striatal dopaminergic homeostasis and leverage this finding to apply [(11)C]-raclopride positron-emission tomography (PET) in the intact animal. While methylphenidate and L-Deprenyl correct both striatal dopamine levels on PET imaging and defective attention system function in Nf1 mutant mice, pharmacologic agents that target de-regulated cyclic AMP and RAS signaling in these mice do not. These studies establish a robust preclinical model to evaluate promising agents for NF1-associated ADD. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：333 / 338

页数：6

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