Attention deficit, hyperactivity disorder (ADHD) is one of the most frequently diagnosed disorders in children, adolescents, and adults. Characteristic symptoms of ADHD include increased motor activity levels, impulsivity, and attentional impairments. Inappropriate processing of sensory and environmental stimuli contributes to the observed deficits in impulsivity and attention. These deficits could occur in cortical or subcortical circuits along primary sensory pathways. Amphetamine-like stimulants, such as methylphenidate (MPH, Ritalin), are the primary treatments for ADHD. These medications are effective;however, patients do experience unwanted side effects. In order to more beneficially manage ADHD, more information regarding the underlying mechanisms of the disorder is needed. Methylphenidate has been shown to increase the level of available norepinephrine and dopamine in the brain. At low doses, however, MPH acts primarily to inhibit the reuptake of norepinephrine with little effect on dopamine transmission. Clinically relevant doses of MPH are in the range of acting principally on the noradrenergic system. The goal of the proposed experiments is to examine the effect of MPH and vigilance on sensory signal processing in the lateral geniculate nucleus through the use of single- and multi- unit recording techniques.
Aims 1 and 2 investigate the effect of MPH on neuronal response to visual stimuli in the anesthetized state. A series of adrenergic antagonists will be administered in conjunction with MPH to determine whether alpha or beta NE receptors contribute to observed changes in neuronal activity.
Aim 3 uses microdialysis to directly measure the changes in NE and DA efflux in the dorsal lateral geniculate nucleus during sensory stimulation and MPH administration.
Aim 4 examines the effect of vigilance on neuronal activity in the lateral geniculate of the awake, behaving animal. The results of these studies will contribute to our understanding of the role of norepinephrine in perception, as well as how changes in sensory signal processing affect behavioral performance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH084478-02
Application #
7920793
Study Section
Special Emphasis Panel (ZRG1-F01-S (20))
Program Officer
Churchill, James D
Project Start
2009-07-01
Project End
2010-12-31
Budget Start
2010-07-01
Budget End
2010-12-31
Support Year
2
Fiscal Year
2010
Total Cost
$25,027
Indirect Cost
Name
Drexel University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104