Mutant mice resist morphine's appeal. (Addiction).

Morphine is a powerful painkilling drug with a well-known downside. It has "this nasty side effect of causing addiction if used inappropriately," says neuroscientist Anthony Basile, who recently moved from the National Institutes of Health (NIH) in Bethesda, Md., to the biotech company Alkermes in Cambridge, Mass.

A batch of genetically engineered mice that Basile and his colleagues created could open new ways to blocking morphine addiction. These mice lack a certain so-called muscarinic receptor, a protein on nerve cells that responds to the signal chemical acetylcholine. People and mice have five variants of this receptor. Basile's team focused on the least prevalent one.

Although seemingly normal, the mice without this receptor variant didn't become addicted to morphine after the one or two doses that it takes for typical mice to get hooked. Equally important, the drug's painkilling effect was undiminished, says Basile.

If given morphine long enough, the mutant mice did become addicted. But when deprived of the drug, the animals' withdrawal symptoms--shaking, jumping, teeth chattering--were much less severe than those of other addicted mice going cold turkey.

Basile suggests that if scientists can develop compounds that block this particular receptor variant, providing those blockers along with morphine could prevent addiction to the painkiller. Moreover, such compounds could make it easier for an addict to quit the drug, he says.

Blockers of the muscarinic receptor may help people with other addictions. The mutant mice lacking the receptor resist dependence on cocaine, too.

Unfortunately, Basile says, no one is currently investigating drugs that target the muscarinic receptor. Adds Barry Everitt of the University of Cambridge in England: "Companies have shown very little interest in developing drugs for addiction."--J.T.