Date of Award
Doctor of Philosophy (PhD)
Julie A. Blendy
The opioid epidemic has generated massive societal, economic, and medical consequences over the last 20 years. Opioids, like most drugs of abuse disrupt sleep, and conversely, poor sleep can be a risk factor for opioid use. However, the precise nature of the relationship between opioids and disrupted sleep is not well known. The research presented here serves to further our knowledge of the neurobiological underpinnings of this pathophysiological feedback cycle between opioids and disrupted sleep. First, we model chronic short sleep in mice and use innovative open-source tools to noninvasively and automatically generate data relating to sleep and morphine reward. We then use electroencephalography to show that morphine disrupts sleep during the dark cycle (active period) after 11 days of morphine. We then look to Mu Opioid Receptors (MORs) in the Paraventricular Nucleus of the Thalamus (PVT) as the locus of morphine-induced sleep disturbance. Manipulating PVT MOR expressing neurons transiently blocked morphine-induced wakefulness in the drug group but not general wakefulness in controls. Finally, using the same morphine administration paradigm, we examine the negative affect associated with protracted withdrawal from morphine. We find that the major cellular energy sensor in the brain, Adenosine Monophosphate-Activated Protein Kinase (AMPK) mediates certain behaviors during protracted withdrawal from morphine. This body of work contributes to our understanding of the intersection between sleep and opioids and demonstrates the importance of considering sleep in the treatment of substance use disorders.
Eacret, Darrell Millikan, "Bidirectional Relationship Between Opioids And Disrupted Sleep" (2022). Publicly Accessible Penn Dissertations. 4892.