Addiction's Grip Strengthens During Withdrawal

After quitting, rats' yearning for cocaine grows over time

TUESDAY, July 10, 2001 (HealthDayNews) -- The urge to use cocaine gets stronger, not weaker, in the weeks and months after quitting, a new study says.

Research at the National Institute on Drug Abuse (NIDA) shows that coke-addicted rats become more sensitive to the environmental cues of their suspended habit over time. In other words, cocaine addicts probably are more vulnerable to relapse well after quitting than they are early on, the researchers say.

"This phenomenon helps explain why addiction is a chronic, relapsing disease," says a statement by NIDA Director Dr. Alan Leshner. "Craving is a powerful force for cocaine addicts to resist, and the finding that it persists long after last drug use must be considered in tailoring treatment programs."

An earlier study revealed that the craving for cocaine involves different brain's circuitry than the initial addiction process. Addiction involves dopamine, a key signaling molecule in the brain's reward pathway, while craving appears to be linked to another neurotransmitter called glutamate.

Dopamine is the chemical that controls the "hey, this feels good" response to a drug like cocaine, says Peter Kalivas, professor and chairman of physiology and neuroscience at the Medical University of South Carolina in Charleston. Glutamate, on the other hand, creates the "I-really-need-this-substance" urges that follow.

In the latest study, led by NIDA investigators Jeff Grimm and Yavin Shaham, seven groups of lab rats were allowed to inject themselves with cocaine by depressing a lever in their cages.

After 10 days of drug-use "sessions," accompanied by the conditioning cues of a red light turned on at the start of each session, and a tone-light combination with each successful injection, the animals were denied the drug.

The researchers then sought to learn how environmental cues -- the levers, lights and tones that once signaled the availability of drugs -- would affect the animals' cocaine-seeking behavior. The experiment was designed with the knowledge that similar cravings can be triggered in human addicts by exposing them to familiar cues, like drug paraphernalia, for example.

After just one day of cocaine deprivation, the rats essentially were indifferent to the cues and did not go much out of their way to attempt to get the drug (which wasn't provided anyway). But rats off coke for 60 days pressed the ungiving levers like mad.

"After 60 days of cocaine withdrawal, the rats' motivation to seek cocaine was much stronger than after one day," Shaham says. The situation is similar to that of an addict willing to pay only $10 for a fix the first day after quitting, but up to $90 for the same hit two months later.

The latest study confirms what many addiction therapists already know, but Kalivas says, "It's an important finding that needed to be documented." He says the findings should encourage researchers studying the biochemistry of addiction to look deeper in time for a better understanding of how drugs affect the brain's chemistry.

What To Do: For more about cocaine abuse, try the NIDA. For more on addiction, try the National Center on Addiction and Substance Abuse.

SOURCES: Interviews with Yavin Shaham, Ph.D., investigator, NIDA, Baltimore, and Peter Kalivas, Ph.D., professor and chairman of physiology and neuroscience, Medical University of South Carolina, Charleston; July 12, 2001 Nature
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