Scientists find clues to cocaine's hold on addicts

Wednesday, April 9th 2003, 12:00 am

By: News On 6

Cocaine-addicted rats experience bursts of brain chemical activity just before seeking out their next fix, scientists report in a finding that could open a new avenue for treating human addicts.

When the rats merely heard or saw cues associated with cocaine, their brains pumped out extra doses of the same reward-related chemical that helps produce the euphoria that human users feel.

The rats' brain activity may explain the intense cravings human addicts experience when something reminds them of the drug.

``They're having a miniature high before they even get there,'' said Anna Rose Childress, a professor of psychiatry at the University of Pennsylvania's School of Medicine.

``It acts like a salty potato chip, or the smell of the brownie across the room, the chocolate croissant in the window _ it's a primer, it's a seductive pull.''

The new work may help scientists find drugs that can dampen drug cravings in people who have quit cocaine, said Childress, who was not involved in the research.

She said the findings could also apply to other drugs such as amphetamines, heroin, opium, nicotine and possibly even alcohol.

The rat study is presented in Thursday's issue of the journal Nature by psychologist Regina M. Carelli and chemist R. Mark Wightman of the University of North Carolina in Chapel Hill.

They detected the dopamine pulses in rats using a new technique that makes rapid ``real-time'' measurements of changes in rat's brain chemicals.

The scientists made the rats addicted to cocaine, then implanted an electrode in a portion of a rat's brain associated with drug use. The rodents could receive cocaine by pressing a special bar which activated a pump implanted in them that injected cocaine into their system.

The drug delivery was accompanied by a tone that sounded and a light that turned on in the area where the experiment was unfolding.

When the rats were presented with the light and the tone was sounded, the researchers detected rapid pulses of dopamine in the rodents' brains. Dopamine levels also rose as the rats approached and pushed the bar to receive their fix.

In contrast, rats that had not been addicted to cocaine showed no comparable increase in dopamine levels when exposed to the same cues. That indicates that the dopamine levels increased in response to cues the rats learned to associate with cocaine, Carelli said.

She said the rodent findings may explain bursts of brain activity seen in human addicts when they crave cocaine or see paraphernalia associated with it.

``People had suspected for some time that just the anticipation of receiving cocaine could cause rapid increases in dopamine levels, but no one had been able to accurately measure it,'' Carelli said.

Roy Wise, chief of behavioral neurosciences at the National Institute on Drug Abuse, said although the studies were conducted in rats, rodents have proven to be a good predictor of how humans respond to drugs. ``The same thing is almost certainly happening in humans,'' he said.

Michael Kuhar, a professor of pharmacology at Emery University in Atlanta, called the research ``a technical tour de force'' that will refine models of how the brain acts in cocaine addicts.