His team also tested a related process called long-term depression (LTD). When treated with an LTD stimulus, normal slices of the rat hippocampus experience a 30 to 40 percent decrease in synaptic transmission. But those rats treated with alcohol or anesthetics experienced a complete elimination of LTD. What LTD does is not well understood, but there is evidence suggesting it is important in spatial working memory and adaptation to new environments.

The rats appeared to behave normally in most other ways, and there were no outward signs of brain damage.

"If similar brain damage had occurred in a human infant, it appears there would not be any overt signs that would alert you to it," Zorumski says.

This area of research has repeatedly identified a relationship between certain classes of drugs that inhibit nerve cell activity and damage to the developing brain. Anesthetic drugs tend to work in one of two ways, both of which inhibit nerve cell activity: Either they inhibit excitatory neurotransmission in the brain, or they enhance inhibitory neurotransmission.

The excitatory system that stimulates nerve cells is what scientists call the NMDA glutamate transmitter system. In 1998, Olney and colleague Vesna Jevtovic-Todorovic, M.D., Ph.D., associate professor of anesthesiology at the University of Virginia, discovered that the drug nitrous oxide (laughing gas) works by inhibiting the NMDA glutamate system. Another anesthetic drug known as Ketamine also works by inhibiting the NMDA glutamate system.

Other anesthetic drugs work by enhancing the inhibitory activity of GABA (Gamma Amino Butyric Acid), which is the primary inhibitory transmitter in the brain.

Olney and his colleagues have demonstrated that when the developing brain is exposed to drugs that block NMDA glutamate activity, nerve cells in the brain commit suicide. They also found that drugs that enhance GABA activity can
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Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
13-Feb-2004