For cocaine addicts trying to quit, the challenge lies not just in breaking the habit, but staying off it too. Recovering cocaine addicts are vulnerable to relapsing into drug use, and are more likely to do so after long periods of abstinence than immediately after they stop taking cocaine. Cocaine cravings following an extended withdrawal require the activation of a protein called extracellular-signal regulated kinase (ERK) in a part of the brain involved in motivation and emotion, according to a paper in the February issue of Nature Neuroscience.
Yavin Shaham and colleagues trained rats to press a lever for an intravenous injection of cocaine. They also paired cocaine infusion with specific environmental cues, so that they learned to associate these cues with the drug. The scientists then withheld both cocaine and cocaine-associated cues from the rats for a month. As with human addicts, the rats showed much higher signs of craving when they were exposed to drug-associated environmental cues after 30 days of withdrawal than after one day.
Shaham and colleagues then found that ERK activation in the central nucleus of the amygdala, a brain region known to be involved in motivation and emotion, was necessary for this craving. ERK activation in the amygdala was higher 30 days after withdrawal than 1 day after withdrawal, and blocking ERK activation decreased cocaine-seeking behavior. Moreover, activating ERK 1 day after withdrawal increased the rats' cocaine-seeking behavior. These results identify a specific biochemical pathway in the amygdala underlying this latent craving, giving us insight into the mechanisms of drug relapse.
National Institute on Drug Abuse, Baltimore, MD, USA.
Tel: 410 550 1746
Additional contact for comment on paper:
J. David Sweatt
Baylor College of Medicine, Houston, TX, USA.
Tel: +1 713 798 3107
Also available online.
(C) Nature Neuroscience press release.
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