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Both attraction to pleasure and avoidance of pain motivate compulsive drug users, studies find

IOWA CITY, Iowa -- What causes compulsive drug use -- the pleasure of the high or avoiding the pain of withdrawal?

This question has interested scientists for years. Some say that addicts seek drugs to get the high, others argue that preventing the pain caused by drug withdrawal is the main reason addicts continue to seek drugs. The controversy is more than grist for a lively discussion; only when scientists understand what actually causes compulsive drug use can they effectively help addicts kick the habit.

Dr. Antoine Bechara thinks that both pleasure and avoidance of pain play a role in compulsive drug use, and that both behaviors are controlled by the brain. The two-system hypothesis proposed by the University of Iowa assistant professor of neurology can explain why heroin addicts who have undergone treatment for withdrawal symptoms, such as those who have completed a methadone-treatment program, often relapse.

Bechara developed his hypothesis while studying the brains and behavior of rats addicted to heroin. The drug-seeking behavior of animals addicted to heroin is much like that of humans, and Bechara's work broadens the spectrum of future treatment options for human addicts.

A review of Bechara's work is published in the January issue of the journal Pharmacology Biochemistry and Behavior.

"Clearly, there are two separate pathways in the brain, one that mediates pleasure seeking and one that governs avoidance of dangerous situations," Bechara says. "Both systems are there and they must operate together."

According to Bechara, the pleasure provided by heroin is the reward for the non-addicted person, and it is the activation of this pleasure system that keeps the rat or human coming back for more.

However, the drug high and the motivation to seek that drug are two separate things. Bechara believes the system that drives a person to seek heroin involves a part of the brain called the tegmental pedunculopontine nucleus, or TPP. The TPP is linked to the limbic system -- an area long believed to be involved in pleasure-seeking behavior. While the TPP is not responsible for the heroin-produced high, but it is tied to the pleasure aspect of compulsive drug use because it controls the drive to go find the drug.

"When there is no dependence on the drug, the TPP system predominates, but as the drug user becomes more experienced, physical dependence develops and the drug user experiences withdrawal symptoms," Bechara says.

(more) 2/25/98

A separate brain system predominates when physical dependence develops, according to Bechara. In this second system, the brain chemical dopamine maintains the drug-seeking behavior in order to avoid withdrawal symptoms. Bechara says that when physical dependence has developed, the motivation to avoid pain overrides the motivation to seek pleasure.

These two systems act independently, so that when the dopamine "avoidance" system is quiet after withdrawal symptoms have been treated, the pleasure-seeking TPP system still functions. In fact, Bechara found that even when withdrawal symptoms were alleviated in a fashion analogous to methadone treatment, rats still sought heroin. When TPP activity was suppressed, rats no longer undergoing drug withdrawal stopped seeking heroin, while rats with normal TPP activity continued to take the drug even after withdrawal symptoms had been alleviated.

The fact that the pleasure-seeking system of the brain -- which includes the TPP -- is still operating after withdrawal symptoms have been alleviated explains post-treatment relapse, according to Bechara.

Bechara believes this work suggests that more addicts will break the cycle of addiction if scientists can figure out a way to suppress TPP activity.

"The novelty of this approach is that suppressing TPP activity stops the motivation or the drive to seek heroin, but it does not prevent the good feeling and sensation that one gets from the drug. This is very important," says Bechara, "because addicts may not mind taking a TPP suppressing drug if they are told that it will not prevent them from getting high. The secret is that when addicts take a TPP suppressant drug, they still get high on heroin, but they no longer have the motivation or drive to seek more."

To this end, work is currently being done to determine what chemical or chemicals in the TPP mediate the pleasure-seeking behavior. Identifying these chemicals will allow the development of an alternative treatment for heroin addicts.

2/25/98