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Brain Clues to Cocaine High
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NEW YORK, April 23 (Reuters) -- Researchers have discovered what causes the
intense "high" felt by cocaine users. The new findings may pave the way to
developing drugs that can combat cocaine addiction.
A new study suggests that the sensation of euphoria felt by a cocaine user
comes from the drug blocking brain cells from taking up dopamine -- the
neurotransmitter chemical thought to be involved in movement, sensation,
and the experience of reward.
"The purpose of the study was to understand what are the mechanisms by
which cocaine produces euphoria in human subjects," says Dr. Nora Volkow,
director of nuclear medicine at Brookhaven National Laboratory in Stony
Brook, New York. "The study shows (that) in humans... the ability of
cocaine to disrupt the transport of dopamine back into the cell is
associated with the perception of the 'high.'"
Volkow explains that dopamine is produced at the synapses of brain nerve
cells (neurons), the junctions at which the cells meet. Cocaine interferes
with dopamine "recognition sites" on brain cells, thus blocking any chance
for the neurotransmitter to get taken back into the cell for further
release. This results in higher amounts of dopamine in the brain tissues
for longer periods than normal, which is believed to cause the 'high.'
"The importance of the study is that one of the main strategies to treat
cocaine abusers is the design of drugs that would bind to these recognition
sites for dopamine (and cocaine), and by so doing, interfere with cocaine's
effects," said Volkow.
"This study documents effectively that the 'high' is associated with these
dopamine sites, or transporters. It also documents that cocaine produces a
significant -- a very large -- percentage of blockade, and that was not
known before," she explains. What this means, she adds, is that effective
treatments would need to be given at doses high enough to target all the
dopamine transporter molecules in the brain.
Positron emission tomography (PET) brain scans in 17 cocaine users revealed
images indicating that injections of cocaine at common doses blocked
between 60% and 77% of the dopamine transporter molecules.
By analyzing the PET images together with the volunteers' own reports on
the drug's effects, the researchers were able to document a significant
relationship between the intensity and duration of the high induced by the
cocaine and the concentration of the drug at the transporter sites seen in
the PET scans. In order for the subjects to perceive cocaine's effects, at
least 47% of these sites had to be blocked by cocaine.
In a related study published in the same issue of the journal Nature,
Volkow and her colleagues used PET scans to document "evidence of
significant biochemical abnormalities" in the brains of cocaine addicts.
"More specifically, it shows that the dopamine system is totally
dysfunctional," she says.
According to the researcher, addicts' dopamine systems have less ability to
respond. To get their dopamine systems turned on, cocaine addicts were
given the brain stimulant Ritalin while walking an exercise treadmill.
"Ritalin is known to increase dopamine concentrations, so the PET scans
allowed us to determine what the magnitude of that change was," says Volkow.
"We observed that the response of the cocaine abusers was half that of
normal subjects," Volkow says.
Specifically, compared to nonusers, cocaine users showed reduced dopamine
responses to Ritalin in the striatum, a region of the brain linked to
motivation control and reward. At the same time, they found an abnormal
increase in the level of dopamine response (production) in the thalamus,
which was associated with intense cocaine cravings among the addicts.
"The findings may account for the lack of interest, the lack of energy, and
some of the depressive symptoms that are seen in the cocaine abuser,"
Volkow says.
However, she notes it is unclear if the reduced dopamine response in
cocaine abusers stems from the use of the drug or if it existed before the
cocaine use.
"We cannot rule out if this is an effect of chronic administration of
cocaine as opposed to something related to genetic predisposition," Volkow
says. "It's very likely, ultimately, to be a combination of both."
SOURCE: Nature (1997;386:827-833)
Copyright =A9 1997 Reuters Limited.
http://www.reutershealth.com/news/rhdn/199704/1997042310.html
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