Rats that have kicked a cocaine habit will desperately try to get the drug again if researchers stimulate a memory center in their brains. In contrast, there's little effect if they stimulate the brain area that produces the high itself. The new study shows for the first time where the rat retains the craving for the drug. And it opens up the possibility of new targets for treating addiction.
Attempts to develop new drugs to treat addiction usually focus on the brain's all-purpose "reward" area--a dopamine-rich pathway called the medial forebrain bundle in the rat. But in recent years, scientists have found indications that the reward function operates independently of craving for a drug.
That's now been confirmed by the new study. A team led by neuroscientist Stanislav Vorel of the Albert Einstein College of Medicine in New York City first got rats hooked on cocaine by hitching them to intravenous catheters that delivered a dose of the drug every time they hit one of two levers in the cage. After establishing the rats' drug habit, the researchers made them go cold turkey by substituting a saline solution for the cocaine. Within a week, the rats stopped pressing the levers.
To test what parts of the brain would rekindle the rats' interest in the drug, the researchers stimulated two spots, they report in the 11 May issue of Science. When they buzzed a glutamate-rich part of the hippocampus called the ventral subiculum, the rats furiously pressed the former cocaine lever for 5 minutes or so until it became clear that they weren't going to get a fix. Electrical stimulation of the reward center, in contrast, had no such effect, even though rats happily self-administer those jolts when given the opportunity.
The experiment adds to a picture that has become clearer over the past decade, says Alan Leshner, director of the National Institute on Drug Abuse (NIDA) in Bethesda, Maryland. Addiction entails two separate processes, he says, one of which is the direct result of drug-taking; the other is "the laying down of memory traces," which occurs at a higher level of the limbic system, namely the hippocampus. And new medications targeted at glutamate circuits may be a more direct way than dopamine-related interventions to get at craving.