Chronic cocaine users have a hard time just saying no, and scientists working with addicted rats may have found out why. Even after the animals no longer regularly get the drug, their brains are still buzzing with a protein that seems to maintain the craving. If the results hold up in humans, the protein might provide a novel therapeutic target to fight drug relapse.
In cocaine addicts, the prefrontal cortex, a region important
for behavioral control, responds rapidly to thoughts of coke. Other
stimuli, like thoughts of food or sex, become less important.
Researchers thought this shift in priorities likely involves
changes in neurons that use dopamine, the neurotransmitter of
so-called reward pathways. To investigate, neuroscientist Peter
Kalivas at the Medical University of South Carolina and colleagues
tracked the activity of a key protein known as AGS3. When dopamine
binds to receptors on the surface of a neuron, AGS3 helps relay the
signal to the rest of the cell.The team injected rats with cocaine
for a week--enough to get them addicted--and then cut off their
supply of the drug. For up to 8 weeks afterward, levels of AGS3
were 30% to 100% higher in the addicted rats' brains than in those
of nonaddicted rats. The protein was concentrated in two regions
thought to be involved in addiction: the prefrontal cortex and the
nucleus accumbens. To determine whether the elevated amounts of
AGS3 ups the odds of relapse, the researchers injected nonaddicted
rats with AGS3. When teased with a touch of cocaine, these rats
suddenly began acting like addicts, frantically pressing a bar that
dispenses the drug.On the other hand, blocking AGS3 seemed to cure
addicted rats of their cravings. When proffered the cocaine tease,
these rats didn't go nuts for more, just as if they had never
sniffed cocaine. Taken together, the results suggest that high
levels of AGS3 in cocaine addicts maintain craving for the drug
during withdrawal, the team reports in the 22 April issue of
Neuron. Kalivas adds that his laboratory is looking at
whether AGS3 also plays a role in addictions to other drugs, such
as alcohol.By showing that AGS3 stays abnormally high for months in
the part of the brain needed for voluntary control over behavior,
the study may explain why it's so hard to kick the habit, says
behavioral neuroscientist Ann Kelley of the University of Wisconsin
Medical School in Madison. Drugs that clear out the protein may
prove to be very helpful, she says, but they're likely to be many
years off.Related site
Cocaine
information and resources from the National Institute on Drug
Abuse
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