PRIMATE SCIENCE RESEARCH HIGHLIGHT
"Epilepsy drug may someday help smokers quit "
(by Russell Meyer, WRPRC editorial intern)

A drug developed to treat epileptic seizures suppresses dopamine
levels in baboons given nicotine injections, according to a study
at Brookhaven National Laboratory  in Upton, New York.

The drug, Gamma-vinyl GABA (GVG) may someday be used to help people
stop smoking by reducing the nicotine "high" that results from
smoking, but also by reducing cravings for nicotine. GVG is being
used to treat epilepsy in 60 other countries; it has not been
approved for use in the U.S.

Neuroanatomist Stephen Dewey, Ph.D., reported that Gamma vinyl-GABA
(GVG) effectively blocked nicotine-induced  increases of dopamine
production in baboon brains. This is significant because the
rewarding and reinforcing effect of nicotine can be explained by
its ability to increase dopamine production in the nucleus
accumbens, an important part of the brain's reward pathways. The
dopamine surge caused by nicotine is thought to underlie the "high"
that motivates people to smoke and may be responsible for nicotine
addiction.

Using positron emission techniques, Dewey and a team of researchers
discovered that larger doses of GVG more effectively  suppressed
dopamine production in baboon brains than did smaller doses when
given 2.5 hours prior to the nicotine injections.

To determine whether GVG's suppression of dopamine can have an
effect on nicotine cravings, fellow researcher Charles Ashby, Ph.D.
at St. John's University, New York, conducted conditional place
preference  (CPP) studies using rats.  CPP studies are intended to
reflect the behavioral response in humans subjected to
environmental stimuli that evoke cravings. 

Ashby injected the rats with nicotine while they were in either a
striped or a plain box, so that the effects of the nicotine would
be associated with one of the boxes. After 19 days of nicotine
treatments, the rats were given either a control solution or GVG
and allowed to move freely between the two connected boxes.  The
control rats spent the most time where they had received the
nicotine, but rats given GVG did not display a preference between
the boxes. The results of the CPP tests strongly suggest that GVG
could be used to reduce nicotine cravings by habituated smokers.

Although GVG is not addictive and does not affect eating habits,
its application for treating nicotine addiction in the near future
must be carefully examined in human volunteers.  Clearly there are
other brain regions and perhaps even other neurotransmitters
associated with addiction. In fact, Dewey reported that dopamine
changes in brain regions other than the nucleus accumbens may
account for "the addictive liability of a particular drug."  He
also reported that neurotransmitters other than dopamine may "play
a vital role" in nicotine addiction. Brookhaven researchers are
conducting more studies to evaluate the effects GVG has in other
brain regions and on other neurotransmitters.

###

References:
Dewey, S., J. D. Brodie, M. Gerasimov, B. Horan, E.L. Gardner, and
C.R. Ashby, JR. 1999.  A Pharmacologic Strategy for the Treatment
of Nicotine Addiction.  Synapse. 31:76-86.

Wickelgren, I. 1998. Drug May Suppress the Craving for Nicotine. 
Science. 282:1797,99



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P-T Research Highlights appears every other week and focuses
broadly on research involving non-human primates. Coverage includes
biomedicine, behavior, conservation and veterinary science. Please
submit highlights for this column to Larry Jacobsen, P-T Research
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supported by a grant from the National Institutes of Health,
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Wisconsin Regional Primate Research Center. No portion of this highlight
may be copied or redistributed without the consent of the editor.

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