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Strength of cocaine cravings linked to brain response

DALLAS March 14, 2006 Rats that have a strong craving for cocaine have a different biochemical response to the drug than their less-addicted counterparts, researchers at UT Southwestern Medical Center have found.

The difference lies in the pleasure-seeking area of the brain, according to a study available online and appearing in a future issue of the journal Neuropsychopharmacology.

"This work shows that there are profound alterations in the brain mechanisms that regulate motivated behavior with addiction," said Dr. David Self, associate professor of psychiatry at UT Southwestern and senior author of the paper.

"It really shows that the addicted person is ill-equipped to cope because the brain is now wired to make them crave drugs more and get less satisfaction out of the drug or other life events that may be rewarding, and this study found biological changes that would explain these behavioral changes," said Dr. Self, who holds the Wesley Gilliland Professorship in Biomedical Research.

The researchers looked at dopamine receptors molecules on cell surfaces that are activated when dopamine or other molecules bind to them. They focused on two types of receptors called D1 and D2.

Molecules that activate D1 are believed to decrease the craving response, while D2 activators are believed to increase it. Both of the receptors bind to the neurotransmitter dopamine in a part of the brain called the mesolimbic dopamine system.

In the study, rats had tubes surgically implanted that fed into their bloodstream, through which they could give themselves cocaine injections by pressing a lever. Some rats voluntarily gave themselves higher doses of cocaine than others did, an indication that they were more addicted to the cocaine.

The rats then went through three weeks of cocaine withdrawal, during which time they ceased to press the lever. At the late stages of withdrawal, a drug that specifically activated the D2 re
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
14-Mar-2006


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