That electric feeling  pg. 3

"We're dealing with a syndrome with many, many complexities and variable presentations.  We need to be able to categorize subjects better.  And one way to do that would be if we could link their genetics with the risk for this disorder, and link more than their genetics, link specific biochemical pathways."
Randy Blakely, Ph.D., director of the Center for Molecular Neuroscience and Allan D. Bass Professor of Pharmacology at Vanderbilt.
Photo by Dean Dixon
Psychostimulants like cocaine, amphetamines and methylphenidate (Ritalin, etc.) are thought to act primarily on the dopamine transporter to increase the supply of dopamine in the synapse. In the average person, however, the results are less desirable: hyperactivity, impaired cognitive function and, potentially, addiction.

Children with ADHD have a paradoxical response to methylphenidate – they become less hyperactive, not more. They are better able to pay attention and are less impulsive, and they don’t become addicted to the drug. This suggests that there’s something different about their dopamine transporter, or about the complex interplay of molecules that carry dopamine messages through their brains.

And this is where the new science comes in.

ADHD appears to be highly heritable – meaning that it tends to run in families, especially when the disorder persists into adolescence and adulthood. Scientists believe that genetic mutations or variations may be involved, at least in some “subtypes” of ADHD.

The search for ADHD genes began with the observation that the drugs used to the treat the disorder act primarily on the dopamine system. To date, the strongest candidates are the genes for the D4 dopamine receptor and the dopamine transporter, for which variations, also called polymorphisms, have been found in studies of children with ADHD and their families.

Paying attention
To test the reaction time of a genetically engineered mouse that displays ADHD-like behaviors, Michael McDonald, Ph.D. and his colleagues at Vanderbilt University Medical Center shine brief flashes of light through one of three holes in the mouse's cage. 
By sticking his nose into the lighted hole, the mouse breaks an invisible infrared beam, triggering the release of a food pellet into the tray behind him.
Because the genetically engineered mice have difficulty paying attention compared to normal control mice, they have slower reaction times, fewer correct responses and, as a result, they are rewarded less often.
Illustrations by Dominic Doyle

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