October 8, 1999

Investigator probes molecular basics of drug addiction

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Danny Winder, Ph.D., is studying the molecular underpinnings of drug addiction. (photo by Dana Johnson)

Investigator probes molecular basics of drug addiction

A Whitehall Foundation grant for neurobiology will accelerate the research program of a new Vanderbilt University Medical Center faculty member.

Danny Winder, Ph.D., assistant professor of Molecular Physiology and Biophysics, received the three-year grant to study the molecular underpinnings of drug addiction.

Winder will focus on the nucleus accumbens, a brain region implicated in addictive behaviors. A variety of studies have shown that this region is critical in the self-administration of drugs of abuse. Difficulty in isolating the nucleus accumbens, however, has hindered its molecular study.

Winder will now apply genetic and electrophysiological techniques to study synaptic plasticity — the changing connections between neurons — in the nucleus accumbens.

"The idea is that persistent changes in animal behaviors, like drug addiction, are caused by lasting changes in brain function at the cellular level," Winder said.

The most well-characterized example of a lasting change in neuronal communication is known as long-term potentiation (LTP). LTP, thought to reflect the cellular changes that underlie learning and memory, has been extensively studied in an area of the brain called the hippocampus.

Winder investigated LTP in the hippocampus during his postdoctoral fellowship with renowned neuroscientist Dr. Eric Kandel at Columbia University. He believes that similar cellular changes in the nucleus accumbens could play an important role in drug addiction.

"It seemed to me that many of the questions we were asking and techniques we were using to study the hippocampus were applicable to other brain regions," Winder said. "It's known that LTP can be elicited in the nucleus accumbens, but that's it. Otherwise, the investigation of LTP in this region is wide open."

After establishing which signaling pathways participate in LTP in the nucleus accumbens, Winder will use genetically modified mice to examine how disrupting LTP in this region affects addictive behavior. He will use a technique he helped develop, the tetracycline-transactivator system, to control where and when genes turn on or off in transgenic mice.

"We will try to make mouse models that can help us understand how people become addicted to drugs," Winder said. "If we understand the molecular and neural circuits that underlie this pathophysiology, then we have a better chance of developing pharmaceutical interventions."

To study addictive behaviors in mice, Winder will utilize the Murine Behavioral Core Facility that is currently being established by Michael McDonald, Ph.D., assistant professor of Pharmacology.

"One of the things that attracted me to Vanderbilt was the behavioral core. Having someone to collaborate with us or show us how to perform behavioral protocols is very valuable," Winder said. "The transgenic mouse core was another big attraction."

Dr. Mark A. Magnuson, professor of Molecular Physiology and Biophysics and Medicine, directs the Transgenic Mouse/ES Cell Core.

Winder joined the Vanderbilt faculty in May. He received his Ph.D. in 1995 from Emory University, where he worked with Jeffrey Conn, Ph.D. The Whitehall Foundation grant is his first grant as an independent investigator.

The Whitehall Foundation is a non- profit corporation focused on assisting basic research in vertebrate (non-clinical) and invertebrate neurobiology. The foundation awards between 30 and 40 grants annually.