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Invited Symposium: What Can Genetic Models Tell Us About Attention-Deficit Hyperactivity Disorder (ADHD)?






Abstract

Introduction

Materials & Methods

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The Coloboma Mouse Mutation as an Animal Model of ADHD

Wilson, MC (Department of Neurociences, University of New Mexico, USA)

Contact Person: Michael c. Wilson (mwilson@salud.unm.edu)


Abstract

Hyperkinesis and developmental behavioral deficiencies are cardinal signs of Attention-deficit Hyperactivity Disorder. In mice, the mutation coloboma (Cm) corresponds to a contiguous gene defect that in heterozygotes (Cm/+) results in overt phenotypic abnormalities including behavioral defects of spontaneous hyperactivity, head-bobbing, and ocular dysmorphology. In addition, Cm/+ mutants are delayed in achieving complex neonatal motor abilities and exhibit deficits in hippocampal physiology which may contribute to learning deficiencies. The hyperkinesis of these mutants is ameliorated by low doses of the psychostimulant d-amphetamine and can be rescued genetically by a transgene encoding SNAP-25, whose gene is located within the Cm deletion. SNAP-25, together with syntaxin and synaptobrevin/VAMP, constitute a core protein complex integral to synaptic vesicle fusion and neurotransmitter release. Despite the ubiquitous role of SNAP-25 in synaptic transmission, and uniformly decreased expression in the mutants, Cm/+ mice exhibit marked deficits in Ca2+-dependent dopamine release, and to a lesser extent 5-HT, selectively in striatum, but not ventral nuc. accumbens. This suggests that SNAP-25 haplo-insufficiency reveals a specific vulnerability of the nigrostriatal pathway that regulates motor activity, and importantly may also provide a model for impaired striatal input affecting those executive functions encoded by the prefrontal cortex which have been associated with ADHD.

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Presentation Number SAwilson0247
Keywords: Neurotransssion, Dopamine, SNAP-25, ADHD, Striatum


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Wilson, MC; (1998). The Coloboma Mouse Mutation as an Animal Model of ADHD. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/sadile/wilson0247/index.html
© 1998 Author(s) Hold Copyright