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Award bolsters study of alcohol’s impact on the brain

Jul. 28, 2016, 10:50 AM

Vanderbilt University researcher Danny Winder, Ph.D., has received a MERIT Award from the National Institute of Alcohol Abuse and Addiction (NIAAA), part of the National Institutes of Health, for his contributions to understanding how alcohol affects the brain.

Danny Winder, Ph.D.
Danny Winder, Ph.D.

Winder is professor of Molecular Physiology and Biophysics, Pharmacology and Psychiatry in the Vanderbilt University School of Medicine. In his lab at Vanderbilt University Medical Center (VUMC), he studies the effect of chronic alcohol exposure and withdrawal on signaling pathways that regulate mood.

His research could set the stage for the development of new treatments for mood and anxiety disorders that are induced by withdrawal from alcohol, and which make it difficult for many alcoholics to remain sober.

“I’m very grateful to NIAAA for giving my lab this opportunity to engage in more high-risk work, and to Vanderbilt for the colleagues, infrastructure and support that make our work possible,” Winder said.

Winder’s grant, which will be extended by the MERIT Award, focuses on stress-reward interactions that may mediate behavioral responses to chronic alcohol exposure. It provides about $350,000 in support annually and is now in its sixth year.

According to the NIH, the MERIT (Method to Extend Research In Time) Award provides long-term grant support to investigators “whose research competence and productivity are distinctly superior.” As long as criteria of excellence are met, they are freed for up to 10 years from the competitive grant renewal process.

Winder earned his Ph.D. in Neuroscience from Emory University in Atlanta, where he worked with Jeffrey Conn, Ph.D., who now directs the Vanderbilt Center for Neuroscience Drug Discovery. After a postdoctoral fellowship at Columbia University with Nobel laureate neuropsychiatrist Eric Kandel, M.D., Winder joined the Vanderbilt faculty in 1999.

Among other findings, Winder and his colleagues have demonstrated that chronic intermittent alcohol exposure up-regulates signaling through the corticotrophin-releasing factor receptor (CRFR), which is involved in the body’s stress response.

Through an action on NMDA receptors in non-synaptic locations, it also enhances a lasting change in neuronal communication known as long-term potentiation (LTP), which may help explain why alcoholism and addiction are so difficult to overcome.

Recently, Winder and his colleagues reported that ketamine, an anesthetic drug that blocks the NMDA receptor and which has been shown to have rapid and long-lasting antidepressant effects in humans, reversed depressive-like symptoms in a mouse model of alcohol withdrawal.

To understand this phenomenon better, they are now trying to identify the specific neural circuits in mice through which ketamine acts.

If those circuits are found to be impaired in human alcoholics who experience withdrawal-induced depression, restoring normal functioning potentially could prevent relapse, he said.

“Danny’s recent work on the role of CRF and the NMDA receptors in alcohol-induced depressive behaviors raises exciting opportunities to understand alcohol addiction,” said Lawrence Marnett, Ph.D., dean of Basic Sciences and Mary Geddes Stahlman Professor of Cancer Research.

“The MERIT award will enable him to focus intently on the molecular and cellular mechanisms linking alcohol consumption and withdrawal with these signaling axes,” Marnett said. “Danny’s research is a great example of the impact of high-quality basic science on a major societal problem.”

Winder is the second Vanderbilt scientist to receive a MERIT Award from the NIAAA. David Lovinger, Ph.D., who also studies the action of alcohol in the brain, received one in 2000. Lovinger currently is chief of the Laboratory for Integrative Neuroscience at NIAAA.

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