Dec 6, 2006    #171
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Neuroscientist uncovers brain mechanism connected to drug addiction Discovery could lead to new drug addiction treatments, prevention Study published in respected neuroscience journal

University of Missouri-Kansas City (UMKC) School of Medicine neuroscientist John Q. Wang, M.D., Ph.D., and his team of researchers have uncovered a connection between glutamate receptors in the brain and the euphoric effect of cocaine.

Neuron, a high impact peer-reviewed neuroscience journal, has published his important study and may be viewed on Neuron's Web site, entitled Modulation of D2R-NR2B Interactions in Response to Cocaine.

Wang, professor of anesthesiology and Westport Anesthesia/Missouri Endowed Chair in Anesthesiology Research, has identified the NMDA subtype of glutamate receptors as an important link for psychostimulants, such as cocaine, to modify excitability of striatal neurons and to stimulate behavioral activity in animal experiments.

“We found a new type of reaction between G-protein-coupled dopamine D2 receptors and ligand-gated ion channel glutamate receptors (NR2B subunits),” Wang said. “The interaction between these receptors is direct and exists in a specific population of striatal neurons and the interaction can be increased by cocaine, producing a euphoric affect. If you block the interaction, then you block the cocaine effect.”

Now that a specific glutamate receptor subtype has been located and associated with drug addiction, the next step is to evaluate the role of the NMDA receptors in different models of cocaine and amphetamine addiction.

Ultimately, the goal is to use the information to find new treatments for drug addiction and possibly answers on how to prevent drug addiction from occurring in the first place.

Wang said there is no way to put a time frame on the project, but addiction research can progress at a hastened pace because of the importance and the large sum of money the federal government has placed on it.

The National Institutes of Health (NIH) gave over $1 million for this study.

Collaborating investigators include Xianyu Liu, Ph.D., postdoctoral research associate in Wang’s lab; Zhigang Xiong, M.D., Ph.D., with Robert S. Dow Neurobiology Laboratories in Portland, Ore.; Fang Liu, Ph.D., at the University of Toronto; and Kim Neve, Ph.D., at Oregon Health and Science University in Portland, Ore.

Sleep effect of anesthesia

In addition to the study on drug addiction, Wang’s lab has been studying the pharmacological mechanisms of anesthetic drugs and their effects. This study explores propofol, a widely used intravenous anesthetic drug, and how it causes a person to sleep.

The traditional view is that these drugs produce anesthesia through activating inhibitory GABA receptors in the brain. Wang’s team found that propofol may also inhibit excitatory glutamate receptors and thereby suppresses glutamate receptor-dependent activation of the ERK pathway, a key intracellular signaling pathway in learning and memory.

“This effect might explain why intravenous anesthetic drugs cause impaired memory in some patients,” Wang said.

This study is published in the current issue of Anesthesiology, a top peer-review journal in the anesthesiology discipline. A color figure from Wang’s article is featured on the cover.

“Dr. Wang’s work represents the best of translational research — bringing the new basic science discoveries to bear on human health problems,” Betty Drees, M.D., UMKC School of Medicine dean, said. “Such work will continue to be a major emphasis of the new UMKC Institute of Translational Research announced by Chancellor earlier this year.”

Wang has been exploring the cellular and molecular devices that produce drug addictive traits for 13 years. He is a graduate of Shanghai Medical College, one of China’s most prestigious medical schools.

He joined the UMKC School of Medicine as an endowed chair in 2004. Before that, he served six years in the UMKC School of Pharmacy.

He has established a research program renowned for its work in addiction research. His laboratory is considered one of the leading addiction research labs in the country.

In all, Wang’s work has been supported by more than $6 million in research grants. Researchers from his lab have published more than 140 articles and more than 110 abstracts. Residents working in his lab have presented their abstracts at national meetings.

His work has led to his book, “Drugs of Abuse: Neurological Reviews and Protocols,” a collection of basic techniques for the neurological study of abusive drugs.

He is the recipient of the UMKC 2006 Trustees’ Faculty Fellow award, which honors scholars for a sustained nationally and internationally recognized record of research and/or creativity.

UMKC, one of four University of Missouri campuses, is a public university serving more than 14,000 undergraduate, graduate and professional students. UMKC engages with the community and economy based on a three-part mission: visual and performing arts, health sciences, and urban affairs.

The UMKC School of Medicine offers a combined baccalaureate/doctor of medicine degree program that admits students out of high school. The program provides students with early and ongoing clinical experience through teams of students, physicians and other health-care providers. The School of Medicine also offers residency training in 15 specialties and 26 subspecialty residency programs. The school partners with Children’s Mercy Hospitals and Clinics, Saint Luke's Hospital of Kansas City, Truman Medical Centers, Western Missouri Mental Health Center and the Kansas City VA Hospital. For more information on the UMKC School of Medicine, visit


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