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Sleep Regulates Incubation of Cocaine Craving
Chen B, Wang Y, Liu X, Liu Z, Dong Y and Huang Y
Journal of Neuroscience, 35: 13300-13310, 2015

After withdrawal from cocaine, chronic cocaine users often experience persistent reduction in total sleep time, which is accompanied by increased sleep fragmentation resembling chronic insomnia. This and other sleep abnormalities have long been speculated to foster relapse and further drug addiction, but direct evidence is lacking. 

In an article published in the Journal of Neuroscience, Drs. Yanhua Huang and colleagues reported that after prolonged withdrawal from cocaine self-administration, rats exhibited persistent reduction in nonrapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep, as well as increased sleep fragmentation. In an attempt to improve sleep after cocaine withdrawal, the authors applied chronic sleep restriction to the rats during their active (dark) phase of the day, which selectively decreased the fragmentation of REM sleep during their inactive (light) phase without changing NREM or the total amount of daily sleep. Animals with improved REM sleep showed decreased incubation of cocaine craving, a phenomenon depicting the progressive intensification of cocaine seeking after withdrawal. In contrast, experimentally increasing sleep fragmentation after cocaine self-administration accelerated the development of incubation of cocaine craving. Incubation of cocaine craving is partially mediated by the progressive accumulation of calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). After withdrawal from cocaine, animals with improved REM sleep showed reduced accumulation of CP-AMPARs in the NAc, whereas increasing sleep fragmentation accelerated NAc CP-AMPAR accumulation. 

These results reveal a potential molecular substrate that can be engaged by sleep to regulate cocaine craving and relapse, and demonstrate sleep-based therapeutic opportunities for cocaine addiction.

Contributors:
Bo Chen, PhD, Xiaodong Liu, PhD, Zheng Liu, PhD, and Yanhua Huang, PhD (Department of Psychiatry, University of Pittsburgh)

Yan Dong, PhD and Yao Wang, PhD (Department of Neuroscience, University of Pittsburgh)

This article appeared online in the Journal of Neuroscience.  Click here to view the abstract.