Journal
EXPERIMENTAL NEUROLOGY
Volume 232, Issue 2, Pages 333-338Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2011.09.005
Keywords
Dopamine; Behavior; Neurofibromin; Cyclic AMP; RAS
Categories
Funding
- National Cancer Institute [U01-CA141549]
- Department of Defense [NF093033]
- National Institute of Child Health and Human Development Center [P30 HD062171]
- Mallinckrodt Institute of Radiology
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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.
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