raclopride and Neurofibromatosis-1

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.

Topics: Animals; Attention; Attention Deficit Disorder with Hyperactivity; Carbon Radioisotopes; Corpus Striatum; Dopamine Antagonists; Dopamine Uptake Inhibitors; Dopaminergic Neurons; Drug Evaluation, Preclinical; Methylphenidate; Mice; Mice, Inbred C57BL; Mice, Neurologic Mutants; Neurofibromatosis 1; Neuroprotective Agents; Positron-Emission Tomography; Presynaptic Terminals; Raclopride; Selegiline