First Author | Brown JA | Year | 2011 |
Journal | Exp Neurol | Volume | 232 |
Issue | 2 | Pages | 333-8 |
PubMed ID | 21963652 | Mgi Jnum | J:178468 |
Mgi Id | MGI:5298435 | Doi | 10.1016/j.expneurol.2011.09.005 |
Citation | Brown JA, et al. (2011) PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice. Exp Neurol 232(2):333-8 |
abstractText | 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. |