In a recent study of mice, researchers from the Department of Psychiatry at the University of Texas Southwestern Medical Center in Dallas found that acute sleep deprivation enhanced the rewarding properties of cocaine use and that blocking the orexin system—the neurons that regulate many body functions, including reward systems—can reduce this effect and mitigate the mice’s drug seeking, especially after experiencing sleep loss prior to drug exposure.
The findings were published in the journal eNeuro.
For the study, adult male mice were placed into three-chambered boxes. Mice were given 20 minutes to explore each of the chambers. Mice that showed an innate preference for a specific chamber were removed. The remaining mice then underwent four trials in which one of three dosage amounts of cocaine or saline with one 30-minute trial per day, followed by a post-conditioning test. The study then compared outcomes for mice on the basis of various degrees of sleep deprivation and the introduction of an orexin-receptor antagonist.
The researchers found that sleep deprivation enhanced cocaine preference in mice in a dose-dependent manner, i.e., the sleep-deprived mice showed a preference for a low dose of cocaine that did not affect rested mice, and they also found cocaine more rewarding than rested mice overall. By introducing the orexin-blocking antagonist, however, the increased cocaine preference shown by sleep-deprived mice was reduced.
The findings suggest that blocking the orexin system can mute the effects of sleep deprivation on drug-seeking behavior.