Scientists identify a brain mechanism underlying persistent cocaine craving

May 28 2008

Scientists have identified a mechanism in the brain that helps to explain why craving for cocaine, and the risk of relapse, seems to increase in the weeks and months after drug use is stopped. The research was supported by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

The study, published in the May 25 issue of the journal Nature, "reveals a novel mechanism for why cocaine craving intensifies over time and suggests a new target for the development of medications to decrease the risk of relapse in abstinent cocaine abusers," says NIDA Director Dr. Nora Volkow.

Exposure to environmental cues (e.g., people, places, things) previously associated with drug use can trigger drug craving, often leading to relapse. Previous research in rats has shown that the sensitivity to these environmental cues follows a defined time course progressively increasing (or incubating) during a 60-day withdrawal period.

In the current study, also in rats, researchers demonstrate that after prolonged withdrawal from cocaine use, there is an increase in the number of proteins called AMPA glutamate receptors in a brain region known as the nucleus accumbens (an area involved in motivation and reward). These new AMPA receptors are atypical - they are missing a particular subunit resulting in greater responsiveness of nucleus accumbens neurons to input from other brain regions - and they appear to be responsible for the 'incubation' of 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," explains lead investigator Marina E. Wolf, Ph.D., Professor and Chair of Neuroscience at the Rosalind Franklin University of Medicine and Science in Chicago.

"The finding suggests," says Volkow, "that 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."

The research was performed in the laboratories of Wolf, Michela Marinelli, Ph.D., and Kuei Y. Tseng, M.D., Ph.D., at Rosalind Franklin University of Medicine and Science, and Yavin Shaham, Ph.D., of the NIDA Intramural Research Program in Baltimore, Maryland.

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to inform policy and improve practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA home page at www.drugabuse.gov.

The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases.