Cocaine Cravings Linked To Brain Response
Article Date: 17 Mar 2006 - 5:00am (UK)
DALLAS March 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
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
"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
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 receptor was given to
see if it would prompt the rats to press the lever
again in search of cocaine. In another experiment, the
rats were given a small dose of cocaine and a drug
that activated the D1 receptor to see if the drug
would block them from seeking more cocaine.
The strongly addicted rats responded more aggressively
to the craving-enhancing D2 activator than the
less-addicted rats did, and were not as strongly
deterred by the D1 activator.
"It's as if the cocaine-addicted animal is less easily
satisfied and more easily induced to seek drugs due to
alterations in these receptors," Dr. Self said.
Before the researchers administered cocaine, the rats
were tested to see how much they moved around when
given D1 or D2 activator drugs. Before getting the
cocaine, their responses to each drug were the same.
After being trained to take the cocaine, the strongly
addicted rats were much more sensitive to the D2
activator but less sensitive to the D1 activator.
These tests showed that the difference in sensitivity
developed during the addiction process, rather than
being already present in the animals from the
The researchers don't know, however, whether the
responses in the rats they studied were due to changes
in the numbers of the receptors or to the biochemical
actions of the receptors already present. Future
research may help clarify those different scenarios,
Dr. Self said.
Understanding how receptors control cravings may be
applicable to humans, although addiction is a
complicated mix of brain biochemistry and learned
responses to environmental cues, as well as stress,
Dr. Self said.
"If people do become addicted and say they want to
quit, their brain system for inhibiting craving is
weaker. We want to try to strengthen those systems
that help them inhibit their craving," he said.
The lead author in the study was Scott Edwards, a
neuroscience graduate student at UT Southwestern.
Other UT Southwestern researchers involved in the
study were Kimberly Whisler, a research associate in
psychiatry, Dwain Fuller, faculty associate in
psychiatry, and Dr. Paul Orsulak, professor of
psychiatry and pathology.
The work was supported in part by the National
Institute on Drug Abuse.
David Self's homepage:
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Contact: Aline McKenzie
Southwestern Medical Center