Mutant mice help shed light on tobacco addiction

Genetically altered mice that are unusually sensitive to nicotine may help scientists nail down exactly how people become addicted to smoking, U.S. researchers said on Thursday.

Specific doorways into brain cells, called receptors, in the newly created mice could hold the key to nicotine addiction, they said. Studying the mice may help in the development of better drugs to help people quit smoking, the researchers wrote in Friday’s issue of the journal Science.

"Nicotine addiction, the largest cause of preventable mortality in the world, leads to 94 million smoking-related deaths annually,” wrote the researchers, led by Andrew Tapper of the University of Colorado and Henry Lester of the California Institute of Technology.

Scientists have known that a family of receptors called nicotinic acetylcholine receptors were involved in addiction to smoking. Lester and colleagues created mice with a mutation in the “alpha4” portion of the receptor that were unusually sensitive to the effects of nicotine.

Brain cells communicate using a neurotransmitter or message-carrying chemical that jumps across gaps between the neurons called synapses. One such neurotransmitter, acetylcholine, activates certain cells to release another neurotransmitter called dopamine, associated with pleasurable sensations.

Once finished, acetylcholine is rapidly broken down by an enzyme called acetylcholinesterase. But nicotine mimics acetylcholine and is not broken down by acetylcholinesterase.

“So it persists at the synapse for minutes rather than milliseconds, and excites the post-synaptic neurons to fire rapidly for long periods, releasing large amounts of dopamine,” Lester said in a statement.

“Most scientists believe that’s a key reason why nicotine is so addictive.”

If a way can be found to stop nicotine from latching on to brain cells, tobacco addiction might be curable.

“It’s a complicated pathway that still must be broken down into individual steps before we can understand it fully, but I personally believe that nicotine addiction will be among the first addictions to be solved, because we already have so many tools to study it,” he said.

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