TY - JOUR T1 - Bidirectional relationship between opioids and disrupted sleep: putative mechanisms JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.119.119107 SP - mol.119.119107 AU - D. Eacret AU - S. C. Veasey AU - J. A. Blendy Y1 - 2020/01/01 UR - http://molpharm.aspetjournals.org/content/early/2020/03/20/mol.119.119107.abstract N2 - Millions of Americans suffer from opiate use disorder, and over a hundred die every day from opioid overdoses. Opioid use often progresses into a vicious cycle of abuse and withdrawal, resulting in very high rates of relapse. While the physical and psychological symptoms of opiate withdrawal are well documented, sleep disturbances caused by chronic opioid exposure and withdrawal are less well understood. These substances can significantly disrupt sleep acutely and long-term. Yet, poor sleep may influence opiate use, suggesting a bidirectional feed-forward interaction between poor sleep and opioid use. The neurobiology of how opioids affect sleep and how disrupted sleep affects opioid use is not well understood. Here, we will summarize what is known about the effects of opioids on electroencephalographic sleep in humans and in animal models. We then discuss the neurobiology interface between reward-related brain regions that mediate arousal and wakefulness and finally summarize what is known of the mechanisms underlying opioid exposure and sleep, as well as the effect of opioids in sleep-related brain regions and neurotransmitter systems. A critical review of such studies, as well as recommendations of studies that evaluate the impact of manipulating sleep during withdrawal will further our understanding of the cyclical feedback between sleep and opioid use.SIGNIFICANCE STATEMENT We review recent studies on the mechanisms linking opioids and sleep. Opioids affect sleep and sleep affects opioid use, however the biology underlying this relationship is not understood. This review compiles recent studies in this area that fill this gap in knowledge. ER -