Studies of rats may help therapy in human addictions

WASHINGTON -- Rats can become drug addicts.

That's important to know, scientists say, and has taken a long time to prove. Now two studies by French and British researchers show the animals exhibit the same compulsive drive for cocaine as people do once they're truly hooked.

Only through experiments with addicted animals can scientists eventually learn what makes some people particularly vulnerable to addiction while others can quit at will, addiction specialists say.

Addicted rats also could help uncover new anti-drug therapies.

Until now, scientists have been able to prove that rats will take drugs, even eagerly, but not that they're actually addicted. The new research was published Thursday in the journal Science.

"What confers susceptibility to experimenting and trying drugs may be quite different than what changes your brain and leads to addiction," explained Terry E. Robinson, a University of Michigan neuroscientist. "These articles provide us the approaches and the techniques to ask the latter."

"There's some fundamental shift" between casual drug use and addiction, added David Shurtleff, chief of basic neurological research at the U.S. National Institute on Drug Abuse. "Your brain has changed and that's manifest as a change in behavior. ... That's something new that's never really been nailed down in an animal model."

Among the ways to know when a rat's hooked: It keeps trying to get cocaine even when each hit comes with an electric shock.

In the French study, rats poked their pointy noses through holes in their cages to trigger injections of cocaine. They were allowed access to the cocaine for three months, much longer than the 10- to 30-day drug-use studies normally done with animals.

Compulsive drug-seeking even in the face of bad consequences is a measure of human addiction. So the researchers devised ways to measure that in animals: routinely cutting off the drug supply and measuring the rats' persistence at poking the supply trigger anyway, seeing how hard they worked to get the drug and noting whether they gave up when their feet were shocked.

Intriguingly, 17 percent of the rats met all three measures and thus were considered addicted -- while roughly 15 percent of human cocaine users become addicts, reported lead researcher Pier Vincenzo Piazza of INSERM, France's National Institute of Health and Medical Research.

The British study focused just on the bad-consequences scenario. Rats who used cocaine for longer periods continued to do so even when their feet were shocked, reported Louk J.M.J. Vanderschuren, who led the study at the University of Cambridge. But rats who had used cocaine for a short period quit once they knew the punishment.

Both studies concluded that extended exposure to cocaine is a key to addiction, but Piazza says that must be combined with some underlying genetic vulnerability -- to explain why all the rats didn't succumb.

"The huge question for the future, then, is what confers the susceptibility," says Michigan's Robinson.