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	From Enjoyment to Dependence


	Addiction to drugs of abuse occurs partly because, over time, the drugs cause long-lasting -- possibly permanent -- changes in the way users' brains experience pleasure and reward. "The problem is these drugs are like a sledgehammer in the brain," says National Institute of Mental Health director Steven Hyman, M.D. "While the person is feeling this euphoria, other things are happening in the brain."


	George Koob, M.D., a professor of neuropharmacology at Scripps Research Institute who has been trying to understand the reward system, thinks that pumping up one's dopamine levels through drug abuse can be likened to overdrawing a bank account. "The system has to self-regulate. If you spend these pleasure neurochemicals in one lump sum, such as with a crack binge, you use up your supply of pleasure for a certain period. You have bankrupted the system. There's no pleasure in your account," says Koob. Then, when the person stops using the drug, they can't feel pleasure -- a state known as anhedonia -- and may experience very negative feelings, such as depression, anxiety, and agitation.

Koob thinks that addicts have compromised their natural pleasure-reward systems in long-lasting ways. Chronic use of a drug to stimulate certain neurotransmitters may reduce the brain's natural ability to produce the neurotransmitters without the drug. People who are addicted initially take the drug because it makes them feel good. But over time they take it just to return to feeling "normal." The "essence of addiction is that a person has created an artificial but negative state," says Koob. The addict is striving to feel stable, not necessarily high, but the effort becomes futile. "After a while the system has become so compromised that a person is taking the drug to return to a normal state. . . . In effect, you spend most of your time not trying to get some extra bliss, but just trying to feel normal," he adds.

-- Janet Firshein

Dopamine Does Not Work Alone: The Role of Other Brain Chemicals

Dopamine is one of the most important neurotransmitters that drugs of abuse affect, but there are other reward neurotransmitters that have been linked with "getting high." Some drugs of abuse, such as the opiates (heroin, morphine), probably also affect endorphins, which are other important neurotransmitters associated with feelings of pleasure. Nicotine has been implicated in activating opiate peptide systems in the brain that release other chemicals affecting mood. A neurotransmitter linked with withdrawal from chronic drug use is corticotropin-releasing factor, or CRF, which is a chemical naturally released in the experience of stress. Koob has found that during acute drug withdrawal, levels of corticotrophin increase, presumably causing feelings of stress.


	Photo: Sue Young Wilson


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