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Rat Studies Elucidate the Neurochemistry of Addiction



Scientists have long wondered what happens in the brain during the moments before a drug addict succumbs to the urge for a fix, or an animal behaves in some other way that it knows will lead to pleasure. But an inability to obtain sufficiently fine-grained measurements of the amount of dopamine--a neurotransmitter associated with feelings of reward--present in the brain has hindered investigations into the neurochemical nature of such cravings. To that end, researchers writing today in the journal Nature describe a novel technique for assessing dopamine levels. The work allowed them to observe instantaneous spikes in the chemical when cocaine-addicted rats were given visual cues that the drug was available.

Paul Phillips and his colleagues at the University of North Carolina surgically outfitted rats with newly developed brain electrodes that recorded dopamine levels 10 times a second--200 times faster than earlier technology permitted. They then trained the animals to associate the pressing of a tiny lever, and the accompanying flash of light and noise, with the pleasure of a hit of cocaine. The team found that brain dopamine surged as the drug-addicted rats turned to walk over to the lever. Levels of the neurotransmitter fell as the creatures approached the lever but then spiked again as they pressed down for a hit. Because the spike was instantaneous, occuring before the cocaine could have reached the brain, Phillips suspected the spike was an anticipatory signal.

To test that theory, the researchers shut off the cocaine pump but continued to place the addicted rats in the same cage. Even though no reward followed when the animals pressed the lever, their dopamine levels shot up when the light flashed and noise sounded.

These findings are the first to measure changes in neurochemistry that lead to pleasure seeking or addictive behavior. "It's a signal in the brain that's highly influential in drug taking," Phillips says. "All that was known before was that dopamine would increase in rats' brains a few minutes after they got cocaine, but there were no specifics to be able to relate this to any particular behavior." Phillips plans to investigate what happens when drug-addicted rats are deprived of cocaine for a period of time and then subjected to the visual cues that they associate with a fix. The hope is to unravel the dopamine cycles that lead to addiction and figure out what causes relapses among those trying to ditch the habit.

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