Insulin's brain impact links drugs an...( Insulin long known as an important r...)

Insulin, long known as an important regulator of blood glucose levels, now has a newly appreciated role in the brain.

Vanderbilt University Medical Center researchers, working with colleagues in Texas, have found that insulin levels affect the brains dopamine systems, which are involved in drug addiction and many neuropsychiatric conditions.

In addition to suggesting potential new targets for treating drug abuse, the findings raise questions as to whether improper control of insulin levels as in diabetes may impact risk for attention deficit hyperactivity disorder (ADHD) or influence the effectiveness of current ADHD medications.

The study, led by Aurelio Galli, Ph.D., in the Center for Molecular Neuroscience and Calum Avison, Ph.D., in the Institute of Imaging Science (VUIIS), appears online this week in the Public Library of Science Biology (PLoS Biology).

The psychostimulant drugs amphetamine and cocaine, as well as related medications for ADHD, block the reuptake of the neurotransmitter dopamine by dopamine transporters (DATs) and increase the level of dopamine signaling. Some of these compounds, including amphetamine, also cause a massive outpouring of dopamine through DATs.

The resulting surge of synaptic dopamine alters attention, increases motor activity and plays an important role in the addictive properties of psychostimulants.

But the link between insulin status and dopaminergic function is not readily apparent.

In the 1970s, there were articles showing that, in animals with type 1 diabetes, psychostimulants like amphetamine would not increase locomotor behavior, said Galli, associate professor of Molecular Physiology and Biophysics. We didnt have a clear understanding of why that was happening.

This sparked Galli and colleagues to investigate the link between insulin signaling and amphetamine action.

Using a rat model of type 1 or juvenile diabetes in which i
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