Addiction clue: just say dopamine.

Addiction clue: Just say dopamine 

Abused drugs appear to share a biochemical event in the sequence of actions they cause in the brain, conclude scientists studying drug addiction. The results of their studies, performed in rats, support the controversial theory that drugs as diverse as alcohol and cocaine feed into the brain's "reward system," setting off a mechanism thought to underlie all forms of drug addiction.

In past experiments, scientists have identified which drugs rats find rewarding by allowing them to self-administer drugs by pushing levers. They found that rats learn quicly to push a lever when it leads to a dose of cocaine, but take longer when it gives alcohol. In recent years, they also have discovered that lesions in a brain area involved in emotion seem to stop rats from pushing the cocaine lever. These experiments and others have convinced many scientists that this area, the nucleus accumbens, is the "hotspot" for the activity of cocaine and amphetamines, and that a chemical called dopamine transmits the rewarding effects. Several researchers have attempted to show that dopamine is critical to all addictive drug pathways, but their experiments have yielded conflicting results. One source of ambiguity may have been that they examined anesthetized animals.

In the recent study, Gaetano Di Chiara and Assunta Imperato of the University of Cagliari, Italy, used a relatively new technique called brain dialysis to measure brain chemicals directly in live, freely moving rats. In the July PROCEEDING OF THE NATIONAL ACADEMY OF SCIENCES (Vol.85, No.14), they describe how they implanted small tubes in the nucleus accumbens and in the caudate nucleus, an area involved in movememt, in rats briefly anesthetized for the procedure. They then administered various doses of addictive and nonaddictive drugs and allowed the rats to move freely. During the following five hours, they periodically extracted fluid from the tubes and measured dopamine levels.

The results show that drugs abused by humans and rewarding to rats -- amphetamine, cocaine, morphine, methadone, ethanol and nicotine -- increased the level of dopamine in both brain areas but significantly more in the nucleus accumbens. These drugs, when in low doses, also caused the rats to run around and to rear. On the other hand, drugs that rats find aversive reduced the concentration of dopamine in both brain areas and, even in low doses, decreased activity. Finally, most drugs not abused by humans, such as antihistamine, had no effect.

Researchers hesitate to make definitive statements about human drug addiction based on experiments in rats, but they say the rat and human systems are close enough that they can draw tentative conclusions. Psychologist Roy Wise of Concordia University in Montreal, Quebec, says the results confirm his theory that dopamine is the common denominator of drug addiction. He adds that the findings show that even drugs classified as depressants can increase physical activity under certain conditions. "All addictive substances can make you want to dance," he says.

Other researchers interpret the results differently. "It's naive to think that all reward takes place through dopamine," says George Koob of the Research Institute of the Scripps Clinic in La Jolla, Calif. Koob says dopamine may act in conjunction with other brain chemicals in response to addictive drugs. That low doses of alcohol stimulated the rats in this study is unusual and probably occurred because the rats were stressed, he adds.