Brain Molecules Behind Nicotine Addiction

Researchers in the 5 November 2004 issue of the journal Science have identified a group of brain receptors in mice that appear to be responsible for the addictive effects of nicotine. These findings may help scientists find targets for drugs aimed to help smokers kick their habit.

"Nicotinic acetylcholine" receptors are expressed in the brain structures thought to be involved in the addiction to smoking. These receptors, which are embedded in the surfaces of neurons, can be composed of different combinations of subunits.

Andrew Tapper and colleagues now report that mice with a mutation in the "alpha4" subunit were unusually sensitive to the effects of nicotine. Compared to normal neurons, the mutant neurons responded to lower concentrations of nicotine and, after this exposure, they also responded more robustly to larger doses. Behavioral tests indicated that mutant mice experienced the basic components of addiction—reward, tolerance and sensitization—at lower doses than normal mice did.

A related "Perspective" raises the question of whether variations in humans' nicotinic receptor genes might determine our susceptibility to addiction.

8 November 2004