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First dopamine whisks you into euphoria // Then compulsion displaces pleasure // Eventually, just the sight of a $20 bill makes your brain scream cocaine // Now, is there any way to replace the brain tissue that got eaten away?

The Addicted Brain

By Anita Slomski // Photographs by James Worrell // Fall 2006
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Drug addiction

James Worrell

Chances are, what’s inside Thomas Stanton’s skull bears little resemblance to a normal brain. Stanton, a 47-year-old medical supply technician at a Veterans Administration hospital in La Jolla, Calif., has been addicted to methamphetamines for 30 years, and the damage such abuse produces tends to be severe. According to Hans Breiter, a psychiatrist who has been studying addicts for 15 years, drugs of abuse significantly remodel brain structures and circuitry, making changes that become apparent when he analyzes magnetic resonance imaging scans. Breiter, whose research will eventually examine the brains of thousands of healthy and addicted subjects, has found in early tests that cocaine addicts who also abuse alcohol have decreased brain volume and diminished cortical thickness in regions that are important for judgment and decision-making. “Preliminary data suggest that parts of their brains are not communicating with other parts,” says Breiter, who directs the Phenotype Genotype Project in Addictions and Mood Disorders at the Massachusetts General Hospital.

For Stanton and other addicts, such brain alterations translate into a habit that’s extremely difficult to kick. Stanton started using meth in the Navy at age 17, when he needed a way to stay alert during long nights standing watch at sea. Since then, he’s been in and out of prison every few years, and though he has been clean for a year and a half, an earlier attempt to quit failed after five years, when loneliness and depression prompted a relapse. He now stays clear of former addict friends to avoid the temptation to get high. “Meth ruined my life, but there are days when I have to do everything in my power not to start again,” Stanton says.

One reason drugs are so alluring, no matter the cost, is well understood. Since the 1970s, scientists have known that the chemical dopamine, unleashed in the brain by all drugs of abuse, is responsible for the euphoria that draws people into addiction. But only recently have researchers discovered more about dopamine’s role—that it facilitates conditioned responses to drugs that result in compulsive abuse even when the drug itself no longer provides pleasure. When dopamine levels get out of kilter, other brain chemicals are also affected, producing profound changes in the circuitry involved with memory, inhibition, motivation and judgment. Treating addiction, scientists have found, requires much more than simply blocking the high.

Drugs of abuse alter a number of neurotransmitters—the chemicals that transmit messages across synapses from neuron to neuron—but their effect on dopamine, which influences circuits that ferry signals of pleasure, awareness, judgment and motivation, may be the most crucial one in causing addiction. Dopamine encourages behavior essential to the survival of the species. It’s released when we eat, quench our thirst or have sex, making us want to repeat those activities. But taking any addictive drug also floods the brain with dopamine, and in much greater quantities than do natural rewards such as food or sex. Animal studies have shown that eating may boost dopamine levels by as much as 50% and that sex doubles them, whereas cocaine can produce triple the normal amount, and methamphetamine causes around a tenfold increase. Moreover, the dopamine surge from addictive drugs lasts longer than a natural high.

This effect begins at the base of the brain, in the ventral tegmental area, from which neurons send their long fibers into the nucleus accumbens, located in the midbrain, and into the frontal cortex. Dopamine attaches to cell receptors in the nucleus accumbens, initiating a cascade of biochemical events inside those neurons, which then pass the signal along to neurons in other brain regions. Normally dopamine is recycled back into the neuron that released it after transmitting its signal to the next neuron. But drugs of abuse disrupt that sequence, either releasing too much dopamine or interfering with its recycling. The chemical pools in the synapses and overwhelms the neurons, producing euphoria.

Because the brain can tolerate only so much dopamine, it may respond to repeated use of cocaine, for example, by reducing the number of a type of dopamine receptor called D2 in the nucleus accumbens. Many addicts have a marked decrease in D2 receptors, although it’s not clear whether they were born with fewer, whether drug use initiated a falloff, or both.

People who are addicted to drugs and have disrupted dopamine systems, including reduced D2 receptors, get fewer rewards from food and sex—for example, the brains of cocaine abusers are stirred by erotica to a much smaller degree than are the brains of healthy subjects—and so the dopamine rush from drugs often becomes the primary source of pleasure. And if repeated drug use further diminishes dopamine receptors, addicts need ever-increasing amounts of a drug to get high.

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1.“Drug Addiction: The Neurobiology of Behaviour Gone Awry,” by Nora D. Volkow and Ting-Kai Li, Nature Reviews/Neuroscience, December 2004. Excellent overview of how addiction occurs, its neurobiology, current and potential pharmacological and cognitive-behavioral interventions, and society’s response to drug abuse.

2.“The Addicted Brain: Overview/The Evolution of Addiction,” by Eric J. Nestler and Robert C. Malenka, Scientific American, Feb. 9, 2004. Pioneering investigators of the molecular basis of drug addiction clearly describe the changes in the brain’s chemistry and architecture as an individual progresses from drug experimentation to intractable addiction.

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