Discovery could help addicts kick the habit
symptoms may be offered relief after researchers were able to
lessen cocaine cravings in rats by blocking signals in their
brains.
The discovery takes a radical step towards finding an effective drug treatment which could help ex-addicts stave off the crippling withdrawal symptoms. Current therapies rely on behavioural techniques such as avoiding tempting situations.
The study, published in Neuron (42, 269 - 281 2004), focused on the brains of cocaine-addicted rats that had been denied the drug for three weeks. The animals were found to have produced increased levels of a brain chemical called AGS3.
Peter Kalivas, chief researcher of the Medical University of South Carolina in Charleston, said: "AGS3 is produced in a region called the prefrontal cortex, which is linked to the brain's motivational circuitry."
"It is the cortex that decides whether you get cravings or not."
The researchers think the compound works by interfering with signalling molecules called G-proteins, which communicate with other brain areas involved in motivation. This fits in with the idea that recovering addicts have skewed interests, for example becoming more excited by their drug than by other pleasures, such as sex.
The researchers tested this theory by injecting the part of the AGS3 molecule that binds to G-proteins into the brains of rats; the animals had previously been trained to press a lever to get cocaine, and were then weaned off the drug.
After being given a further small dose of cocaine, the treated rats pressed the lever more frequently than untreated ones, despite the fact that the drug was no longer available, suggesting that they experienced stronger cravings.
Kalivas's team then set out to see if AGS3 levels could be reduced, in order to alleviate these cravings. They injected into the rats' brains an antisense oligonucleotide - a type of molecule designed to block the production of AGS3. The resultant effect was the rats pressed the lever less often than normal.
Kalivas said: "If AGS3 has a similar role in human brains, such treatment could help tackle addiction."
"If we could find a way to reduce levels of this protein in humans, they would in theory gain a lot more control over their cravings."
John Marsden, an addiction researcher at the Institute of Psychiatry in London, UK, welcomed these findings adding: "So far no drug has been developed that can alleviate the cravings that cripple many addicts."
Marsden explained that the effects of cocaine withdrawal vary widely from person to person. Symptoms include moodiness, lethargy and sleeplessness, and can last as long as a year.
"There have been a lot of blind alleys in looking for anti-craving agents," Marsden says. Addiction therapists currently coach their patients to avoid drugs by stressing the satisfaction gained from remaining clean, and advising them to go for a walk or telephone a friend when the going gets rough.
But Marsden remains confident experts will uncover the molecular secrets of drug problems. "I think we'll see a thorough mapping of the biological basis of addiction in the next decade," he predicts.
During 2001, there were approximately 1,160,000 new cocaine users in the US, the average age of which was 20.8 years. According to the 2002 National Survey on Drug Use and Health, approximately 33.9 million Americans ages 12 and older had tried cocaine at least once in their lifetimes, representing 14.4 per cent of this age group.
