An unusual buildup of brain proteins could be the biological underpinnings of craving for cocaine, according to researchers from the Rosalind Franklin University of Medicine and Science and the National Institute on Drug Abuse (NIDA).

Past research has shown that exposure to environmental cues associated with drug use can trigger craving, and that sensitivity to these cues tends to intensify during the 60 days following the last use of cocaine. The latest study, led by Marina E. Wolf, Ph.D., of Rosalind Franklin University in Chicago, found that during cocaine withdrawal there is an increase in the number of brain proteins called AMPA glutamate receptors in the nucleus accumbens, a part of the brain known to be involved in motivation and reward.

Researchers found that the new AMPA receptor sites that are formed during withdrawal are missing certain components, resulting in the nucleus accumbens becoming more sensitive to input from other brain regions and prompting cocaine craving.

"When these atypical receptors are blocked, cue-induced cocaine seeking during the withdrawal period is reduced. This finding suggests that this increased reactivity of the nucleus accumbens explains the intensified cue-induced cocaine seeking that occurs after prolonged withdrawal," said Wolf.

NIDA director Nora Volkow said the findings suggest a new target for medications designed to prevent cocaine craving. "Medications could be developed to block the atypical AMPA receptors in the nucleus accumbens, thus reducing drug craving, without interfering with neurotransmission at typical AMPA receptors, which are important for normal brain functions such as learning and memory," she said.

The study was published in the May 25, 2008 issue of the journal Nature.