Public release date: 1-Jul-2002
Contact: Robert Conn rconn@wfubmc.edu 336-716-4587
Wake Forest University Baptist Medical Center
http://www.wfubmc.edu/

Wake Forest investigator shows new way that alcohol affects brain

WINSTON-SALEM, N.C. - A Wake Forest University School of Medicine researcher today challenged a commonly accepted view on how alcohol acts in the brain in a plenary session presentation at the Research Society on Alcoholism meeting in San Francisco.

Jeffrey Weiner Ph. D., 2001 winner of the society's Young Investigator Award, said many scientists had thought for years that one of the ways that alcohol works was in much the same way as benzodiazepines (such as Valium and Xanax) or barbiturates (such as Nembutal). "But recent data from our laboratory and others challenge this concept and suggest that alcohol may have more complex effects."

Weiner's work focuses on what is called the GABA synapse which he says contributes to many of alcohol's behavioral and cognitive effects, especially intoxication, dependence and withdrawal. "The GABA synapse is the main inhibitory synapse in the brain."

The synapse is the gap between individual nerve cells in the brain. Nerve cells communicate with each other across these synapses by using chemical transmitters.

GABA is one of several of those neurotransmitters, targeting what are known as GABA receptors. Barbiturates and benzodiazepines act only on these receptors, which is the source of their inhibitory or tranquilizing effect. Anesthetics also work on these receptors, as does alcohol.

But Weiner, a member of Wake Forest's Center for the Neurobehavioral Study of Alcohol, recorded extensive evidence that alcohol also affects the nerve cell in the region before the synapse, which is called a pre-synaptic interaction.

"Unless you really focus on all of these mechanisms, you don't get the full picture of what alcohol is doing," said Weiner, assistant professor of physiology and pharmacology. "By looking at both pre- and post- synaptic mechanisms, we discovered a whole new way that that the sensitivity of the synapse to alcohol is regulated."

That makes alcohol "very different" from the two comparison classes of drugs -- barbiturates and benzodiazepines.

He said that this pre-synaptic activity may open the door for new drugs that might be used to treat alcoholism by focusing on that mechanism. For instance, he has already shown that a chemical called baclofen blocks the effect of alcohol on GABA synapses, but has no effect on benzodiazepines or barbiturates.

"By doing this work, we gained new insight into what determines the overall sensitivity of the GABA synapse to alcohol," said Weiner. "That might help explain some of the individual variability and sensitivity to alcohol and aid in identifying individuals at risk of abusing alcohol."

"Exploiting the targets we have found may aid in the development of pharmacotherapy," he said.

In making the discovery, Weiner made use of a technology that was not widely used until the 1990s, known as the whole cell patch clamp electrophysiological method. The technology lets scientists focus on activity within individual brain cells.

Using the technology in rat brains, Weiner was able to measure and document the variations in sensitivity to alcohol.

The result of his research is a tentative conclusion that alcohol effects on GABA synapses "may involve a complex interplay between pre- and post- synaptic processes and likely differs fundamentally from the effects of other modulators" of these inhibitory synapses.