Drug abuse studies focus on how areas of the brain interact

SAN FRANCISCO - Few 4-year-olds are drug addicts, but most have a similar problem - lack of willpower. You can prove it with Oreo cookies. <br><br>Sit a typical child of 4 at a table with Oreos and offer

Tuesday, April 18th 2000, 12:00 am

By: News On 6

SAN FRANCISCO - Few 4-year-olds are drug addicts, but most have a similar problem - lack of willpower. You can prove it with Oreo cookies.

Sit a typical child of 4 at a table with Oreos and offer a choice - one cookie right now, or two if the kid is willing to wait while the adult in charge leaves the room for a while.

Usually, kids say they'd prefer to wait and get two cookies. So the adult leaves. But an Oreo remains on the table. Most kids cave in and go for the cookie - in less than a minute.

The capacity to defer gratification - and to exert better control over behavior - generally improves with age. Six-year-olds can wait for the adult to return. But drug addicts seem to exhibit the willpower of a 4-year-old, with the self-control of adulthood utterly defeated by a chemical conspiracy inside their brains.

At its most basic, drug abuse is bad behavior, in the sense that the brain makes choices that are not in its owner's best interests. Investigating this drive toward self-destruction has focused on the desire for reward or the need for a fix.

But new research suggests that the power of drugs is much more complicated than simply seeking the pleasure of a rush or escaping the pain of withdrawal. Multiple pathways of information processing in the brain contribute to a drug abuser's loss of control and tendency to relapse.

Scientists say the latest data from inside the brain may offer better explanations of how the brain monitors its behavior and how that monitoring system might go awry. And a major part of addiction, much research indicates, may be governed by the same brain systems involved in normal learning and memory.

"Some work has identified a specific interaction between learning mechanisms in animals and the effects of certain drugs," says Trevor Robbins, a psychologist at Cambridge University in England. "We've identified specific neural circuitry which mediates those effects."

In any case, the abuse of drugs also clearly taps into what some psychologists call the "hot" side of the brain - the circuitry of emotion and impulse. By contrast, the "cool" side counters with intellect and reflection.

Willpower, says psychologist Janet Metcalfe, is all about maintaining cool control over the brain's hot side.

Drs. Metcalfe, Robbins and other researchers discussed recent insights into addiction in San Francisco last week at the annual meeting of the Cognitive Neuroscience Society. The speakers explored evidence provided both by animal studies and experiments with humans, ranging from giving kids Oreo cookies to scanning brain activity in heavy drug users.

Such studies show that addictive drugs stimulate circuits in the brain that predispose people to repeat certain behaviors in order to acquire some reward. Psychologists call the rewards that shape behavior "conditioned reinforcers."

"Most of our rewards in everyday life are conditioned reinforcers," Dr. Robbins noted - praise and money, for example. Many drugs influence the reinforcement system by stimulating release of a brain chemical called dopamine. Certain nerve cells in the midbrain specialize in producing dopamine. Tentacles from those cells squirt dopamine into brain regions involved in seeking reward and choosing actions. Most drugs of abuse enhance the release of dopamine.

And dopamine plays a major role in normal learning and memory. In the current issue of the journal Neuron, neuroscientists Joshua Berke of Boston University and Steven Hyman of the National Institute of Mental Health review recent findings suggesting that the same brain circuits involved in learning ordinary habits may underlie compulsive drug abuse.

Various studies have shown that dopamine release can activate chemical reactions linked to learning. Furthermore, blocking dopamine action can impair certain forms of learning. Drugs such as cocaine, amphetamine, nicotine and even opiates, such as heroin, can affect the dopamine systems related to learning and memory.

"Just as in normal learning, with prolonged drug use the relative role of distinct . . . memory circuits may change," the scientists wrote in Neuron.

Dopamine is not the whole story, however. Some addiction research implicates problems with the common brain chemicals serotonin and norepinephrine.

Dr. Robbins, for example, described experiments with amphetamine abusers showing signs of reduced serotonin activity in the frontal part of the cortex, the brain's wrinkled outer layer.

The frontal cortex is the scene of the brain's higher-level thought processes, such as decision making. It is tied to other brain parts by numerous nerve cell circuits, including feedback loops that pass through the striatum, a region strongly affected by dopamine release from the midbrain. The striatum also receives signals from the brain's cortex, emotional and memory centers, and returns messages to the cortex via a series of brain structures serving as relay stations.

Ultimately, the messages that reach the prefrontal cortex - the region of the brain directly behind the forehead - influence the brain's choice of behaviors. Addiction presumably disrupts the brain's ability to make sound choices.

But the decision-making process is complicated, notes Jonathan Cohen, a psychologist and psychiatrist affiliated with Princeton University and the University of Pittsburgh.

Good decision-making requires control over competing possibilities, Dr. Cohen said at the neuroscience meeting. But it also requires monitoring choices to see whether they produce the desired result. Perhaps addiction involves problems with the monitoring system as well as the control system.

Dr. Cohen described research implicating another part of the cortex, the anterior cingulate, in monitoring the brain's choices. In particular, the cingulate becomes active when people are faced with conflicting choices - such as identifying the color of the word "green" if it is printed in red ink.

The monitoring system may also involve a brain region known as the locus coeruleus, which produces norepinephrine. Addictive drugs may affect the locus coeruleus, interfering with the brain's normal system for monitoring and controlling behavior, Dr. Cohen suggested.

In any event, control over behavior is a central problem in addiction or in loss of willpower in general, such as with Oreos.

"It's obvious that willpower has implications for drug abuse," Dr. Metcalfe, of Columbia University in New York, said at the neuroscience meeting. With her collaborator W.J. Jacobs of the University of Arizona, she has devised an approach to understanding willpower by viewing the brain as composed of two related systems, designated "hot" and "cool."

The hot system is the emotional, "go-for-it" side of the brain, in contrast to the cool, thoughtful, "know-before-you-go" side. The hot system is simple, fast and reflexive; the cool system is complex, slow and reflective. The hot system develops early in life and is triggered by stress; the cool system develops later in life and is turned off by stress.

"High stress shuts the cool system down," Dr. Metcalfe said. And stressful environments are strongly linked to the tendency to abuse drugs.

The trick in willpower is to divert the stimulus for the hot system into the proper part of the cool system, she said.

"Impulsive responses are coming out of the hot system," she said. "We want to capture that activation in the cool system so that response doesn't happen."

Experiments with Oreos and 4-year-olds have demonstrated strategies that help keep the cool side in control. Hiding the cookie in a cookie jar, for example, makes the 4-year-old less likely to eat it as soon as the experimenter leaves the room. About three-fourths of the kids manage to wait as long as 15 minutes if the cookie is in the jar.

Another aid to willpower is distraction - if toys are available, half the kids can wait 15 minutes.

In fact, Dr. Metcalfe observed, mental strategies can even substitute for the physical interventions. Telling the kids to think about playing with toys, or to imagine that the cookie is just a picture of a cookie, also extends the time the kids can wait.

"As one kid put it, 'You can't eat a picture,' " she said.

Applying these lessons to aiding addicts could be complicated, though. Providing distractions, for example, might backfire.

"You have to be quite careful with this in the addiction business," Dr. Metcalfe said, "because there are lots of situations where distracter pleasures are associated with the drug. . . . If cocaine and sex are linked in the environment [of drug use], you may be just leading right back to cocaine" when using sex as a distraction.

In any event, the connections between the hot and cool system, or between the emotional and thoughtful side of human behavior, are clearly central aspects of addiction. But many questions about those connections remain unanswered.

For example, asks Dr. Robbins, do the prefrontal cortex decision-making problems indicate innate defects in the brain leading to drug abuse, or does using drugs damage the decision-making system? He plans new animal experiments to address that question.

Hans Breiter, who reported on experiments scanning the brains of cocaine users, points out that drug users clearly have impaired circuitry governing the link between motivation and action. But does the drug hijack the motivation system, causing drug-seeking action? Or does the drug merely sabotage the behavior control system, diminishing willpower?

Dr. Breiter, of Harvard Medical School in Boston, favors the hijacking hypothesis. But much more research is needed to tell for sure, he said, and to provide a picture of the brain that merges the workings of its emotional and thoughtful sides.

"We have a long way to go," he said. "Perhaps we're beginning to see the tip of the iceberg."