Pubdate: Wed, 9 Oct 2002
Source: Stanford Report (CA Edu)
Copyright: 2002 Stanford Report
Contact:  http://www.stanford.edu/dept/news/report/
Details: http://www.mapinc.org/media/1038
Author: AMY ADAMS

SYMPOSIUM EXPLORES THE SCIENCE OF ADDICTION TREATMENT

Although the fried egg imagery of the 1980s anti-drug advertising campaign 
was less than exact, the ads did get one thing right: a brain on drugs is 
permanently changed by the experience. That's according to research 
presented at an addiction symposium at Fairchild Auditorium Friday.

The symposium, organized by Robert Malenka, MD, PhD, the Nancy Friend 
Pritzker Professor in psychiatry and behavioral sciences, and sponsored by 
the Stanford Brain Research Institute, assembled addiction experts from 
across the country to discuss how drugs alter the brain's chemistry and 
physiology.

"The experience of drug-taking leaves a permanent mark on the brain," 
Malenka said during his presentation. These changes make the brain more 
sensitive to drugs and cause a person to crave drugs. "Drugs lead to 
wanting, not liking," he added.

Scientists' understanding of addiction comes, in part, from new imaging 
technologies that pinpoint regions of the brain that are active when a 
person takes or craves a drug. These images have guided researchers to an 
almond-shaped structure in the brain called the amygdala, which helps 
regulate a person's emotions, and the nucleus accumbens, which is involved 
in the brain's reward and punishment feedback.

Hans Breiter, MD, director of the Motivation and Emotion Neuroscience 
Center at Harvard Medical School, said he sees different regions of the 
brain become active in addicts who receive a drug and addicts who are shown 
pictures of other people receiving the drug. People without an addiction or 
who receive a placebo don't show any activation of those regions. "These 
people clearly had an adapted brain," Breiter said.

Some of the changes that take place in a drug-addicted brain include 
stronger connections between neurons in the nucleus accumbens - one of the 
regions highlighted by Breiter's imaging work. Malenka has found that 
neurons in this region form much tighter connections after he injects mice 
with cocaine rather than a placebo solution. This change lasted for several 
days after the injection.

In addicted mice, the neuron regions that make connections with neighboring 
neurons - called dendritic spines - grow more densely branched and able to 
form connections with more neurons. This change seems to come about when a 
gene called delta FosB becomes active after many months of drug addiction, 
said Eric Nestler, MD, PhD, chair of the department of psychiatry at the 
University of Texas Southwestern Medical Center.

Nestler said several genes are turned on soon after rodents take a drug, 
but that delta FosB becomes active in animals that take the drug 
chronically. He created mice that produce the delta FosB protein in their 
brains even in the absence of a drug. The mice who made delta FosB learned 
how to get cocaine from an apparatus more quickly than their litter mates, 
were more sensitive to cocaine, and were willing to work harder to get the 
drug once they had become addicted.

Nestler added that delta FosB remains in the brain even after an animal has 
been off cocaine for many months, which could explain why an addict has 
such a hard time staying off the drug. "Once it is turned on, delta FosB 
maintains an addiction," Nestler said.

Nestler said this work could lead to treatments. "The goal is to understand 
what causes addiction and prevent it from occurring," said William Mobley, 
MD, PhD, the John E. Cahill Family Professor in the School of Medicine, who 
hosted the morning session.

One step toward a molecular treatment for addiction came from Charles 
O'Brien, MD, PhD, vice chair of the department of psychiatry at the 
University of Pennsylvania, who discussed his studies using the drug 
naltrexone to treat alcoholism. Naltrexone blocks receptors in the brain 
that bind opioids and lead to the pleasurable sensation from alcohol or 
heroin. It has been used since the 1980s to treat heroin addiction.

In a clinical trial, recovering alcoholics who took naltrexone lost the 
craving for alcohol and were less likely to relapse than people taking a 
placebo. People on naltrexone reported less feeling of euphoria when they 
drank than alcoholics who weren't on the drug. The downside is that people 
were likely to relapse when their naltrexone treatment ended. "Naltrexone 
doesn't work if you don't take it," O'Brien said.

"This research is an example of how modern research will make inroads into 
addiction and other serious brain disorders," Malenka said.
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