Dr. Darlene Brunzell,
Assistant Professor, Pharmacology and Toxicology
Nicotine no match for cone snail toxin: VCU School of Medicine
study finds Magician cone snail toxin may one day help smokers quit.
The Magician cone snail is far from your typical garden-variety type of
snail. A predatory sea dweller, this snail packs a cone-shaped shell and
an uncanny knack for hunting. It stalks and paralyzes its prey,
typically fish, with a swift chomp from a specialized tooth that acts as
a poisoned harpoon. While the neurotoxins delivered by its sting may
ultimately do its victim in, researchers at the Virginia Commonwealth
University School of Medicine have found that a component of its toxin
may work a different kind of magic on a set of nicotine receptors in the
brain – which may one day help smokers break the habit.
When a smoker takes a puff from a cigarette the inhaled nicotine acts on
receptors in the brain in an area known as the nucleus accumbens - one
of the areas of the brain associated with control motivation and reward.
The series of events results in the release of neurotransmitters such as
dopamine and makes the brain think it wants more nicotine.
Darlene Brunzell, Ph.D., assistant professor in the VCU Department of
Pharmacology and Toxicology, together with colleagues from VCU and the
University of Utah, have found that a peptide known as alpha conotoxin
MII may reduce motivation to use nicotine in a rat model by blocking the
action of nicotine receptors. MII is a part of the cocktail of toxins
injected by the Magician cone snail into its prey.
According to Brunzell, these are the first studies to make a functional
link between the activity of the MII-sensitive subclass of nicotinic
receptors in this region and behavior that supports nicotine dependence.
Specifically, the team observed that rodents who use daily nicotine lose
their motivation to work for nicotine when their alpha-6 containing
nicotinic receptors were blocked by MII. Brunzell said that these
findings were specific to nicotine and did not affect the rats’
motivation to work for more natural reinforcers.
“Nicotine replacement therapy, and even the drug varenicline, which is
much more selective, hit a wide array of nicotinic receptors that
regulate cognition and emotion in addition to their control of tobacco
use,” explained Brunzell. “MII-sensitive receptors represent a much
smaller pool of these receptors. “If our studies in rats hold true in
humans, blocking MII-sensitive receptors may be sufficient to curb
tobacco use without producing undesirable side-effects in
therapy-resistant smokers,” she said.
The work was supported by grants from the National Institutes of Health.
The study was published in the February 2010 issue of the international
journal Neuropsychopharmacology, a journal of the Nature Publishing
Sathya Achia Abraham: VCU Communications and Public Relations