May 27, 2003 Brain changes that occur with cocaine use and the tendency toward relapse may be reduced by a behavioral treatment using extinction training--a form of conditioning that removes the reward associated with a learned behavior. NIDA-funded researchers found that extinction training during cocaine withdrawal produces changes in brain receptors for glutamate, a brain chemical found in the nucleus accumbens, the reward center of the brain. A reduction in glutamate input from cortical brain regions by chronic cocaine use is thought to contribute to persistent cravings for the drug.
The researchers trained rats to self-administer cocaine by pressing a lever and to associate the availability of cocaine with certain environmental cues (lights and noise). Once the rats had learned to expect cocaine when they pressed the lever, cocaine and the cues were removed so that the rats did not receive the cocaine that they were anticipating. One group of rats received this extinction training during cocaine withdrawal while another group did not receive the training. After extinction training was over, the researchers exposed the rats to the cocaine-associated cues and administered cocaine to induce relapse.
The researchers found that the rats given extinction training during withdrawal had more than a 30 percent increase in glutamate receptors in the outer regions of their nucleus accumbens. The number of glutamate receptors did not increase in rats that did not receive the training during withdrawal. When cocaine-related cues were reinstated, rats showing relatively no response to these stimuli had a greater increase in receptors than rats that responded to the cues.
These findings indicate that behavioral-based treatment approaches have the potential to reverse or lessen the harmful neurobiological and behavioral consequences of chronic drug use. Increasing the number of glutamate receptors may help ease cravings for cocaine during abstinence and also help prevent relapse.
This study was published by lead investigator Dr. David Self at the University of Texas Southwestern Medical Center in the January issue of Nature.
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