ANTIEPILEPTIC DRUG BLOCKS RATS' TASTE FOR NICOTINE

Scientists from the USA have discovered that the antiepileptic drug
vigabatrin can block drug-seeking behaviour in animals by increasing brain
concentrations of GABA (-aminobutyric acid). If this effect is also found
in people, vigabatrin could be one way to tackle addictions, including
addiction to nicotine.

In the USA, 35 million smokers will try to quit each year. But more than
70% of attempts are unsuccessful and chronic use of nicotine replacement to
combat nicotine addiction may be harmful.

Stephen Dewey (Brookhaven National Laboratory, Upton, NY, USA) and
co-workers previously found that vigabatrin lowered cocaine-induced
dopamine release in the brain, and abolished drug-seeking behaviour in
cocaine-addicted animals (see Lancet 1998, 352: 1290 ). Because nicotine,
like other addictive drugs, increases synaptic dopamine in areas of the
brain related to reward, the team hypothesised that vigabatrin might also
disrupt the rewarding effects of nicotine.

The investigators now report that vigabatrin blocks nicotine-induced brain
dopamine release in rats and primates. Further, vigabatrin treatment
disrupts rats' preference for an environment previously associated with
nicotine; pretreatment with the drug blocks the development of such a
preference. These findings suggest that vigabatrin abolishes the
motivational effects of nicotine (Synapse 1998; 81: 76-86). Importantly,
the dose of vigabatrin that blocks these behaviours in rats is equivalent
to less than a tenth of the standard antiepileptic dose in people, says Dewey.

Dewey and colleagues have found that vigabatrin also blocks the biochemical
and behavioural effects of alcohol, morphine, amphetamine, and
methamphetamine in animals. "It's quite unique that one drug appears
effective for many different drugs of abuse whose ability to elevate
dopamine is via a host of different mechanisms", he says. So, targeting the
GABA neurotransmitter system could be a fundamental strategy for tackling
addiction, he adds.

Clinical trials in smokers and in cocaine addicts are planned, which "could
be started within 6 months if US approval [of vigabatrin] goes smoothly",
says Dewey.

Checked-by: derek rea