Chronic Sleep Deprivation Blocks Voluntary Morphine Consumption but Not Conditioned Place Preference in Mice.

Darrell Eacret,Jasmine I Caulfield,Sigrid C Veasey,Crystal Lemchi,Sonia A Cavigelli,Julie A Blendy

doi:10.3389/fnins.2022.836693

Abstract

The opioid epidemic remains a significant healthcare problem and is attributable to over 100,000 deaths per year. Poor sleep increases sensitivity to pain, impulsivity, inattention, and negative affect, all of which might perpetuate drug use. Opioid users have disrupted sleep during drug use and withdrawal and report poor sleep as a reason for relapse. However, preclinical studies investigating the relationship between sleep loss and substance use and the associated underlying neurobiological mechanisms of potential interactions are lacking. One of the most common forms of sleep loss in modern society is chronic short sleep (CSS) (<7 h/nightly for adults). Here, we used an established model of CSS to investigate the influence of disrupted sleep on opioid reward in male mice. The CSS paradigm did not increase corticosterone levels or depressive-like behavior after a single sleep deprivation session but did increase expression of Iba1, which typically reflects microglial activation, in the hypothalamus after 4 weeks of CSS. Rested control mice developed a morphine preference in a 2-bottle choice test, while mice exposed to CSS did not develop a morphine preference. Both groups demonstrated morphine conditioned place preference (mCPP), but there were no differences in conditioned preference between rested and CSS mice. Taken together, our results show that recovery sleep after chronic sleep disruption lessens voluntary opioid intake, without impacting conditioned reward associated with morphine.

Highlights

Sleep is an essential biological function that has many roles in maintaining the health of an organism, and better sleep quality is beginning to be emphasized in education and medicine (Eban-Rothschild et al, 2017; Ramar et al, 2021)
We provide the first study of long-term sleep disruption on morphine intake and reward in mice
Our sleep deprivation period restricts sleep by 25% during the light cycle over the total time course of the experiment, and as NREM and REM total sleep time are associated with corticosterone regulation more strongly in the light cycle than the dark cycle (Nollet et al, 2019), sleep disruption during the normal inactive period of the animal would be more robust than sleep disruption during the active period

Summary

INTRODUCTION

Sleep is an essential biological function that has many roles in maintaining the health of an organism, and better sleep quality is beginning to be emphasized in education and medicine (Eban-Rothschild et al, 2017; Ramar et al, 2021). Two nights of sleep disruption (20 min awakening per hour and one random 60 min awakening) decreased the analgesic effect of morphine in healthy adult subjects (Smith et al, 2020) Taken together, these studies show a central interaction between sleep deprivation and opioid signaling. We used an established model of CSS (Zhu et al, 2018) with non-invasive sleep (behavioral quiescence) recording and automated drinking sensors to assess the effect of prolonged sleep disturbance on both voluntary consumption and associative rewarding properties of morphine in male mice. This sleep deprivation did not affect corticosterone levels or affective behavior, but did increase Iba expression, in the hypothalamus. These data represent, to the best of our knowledge, the first investigation of extended sleep deprivation as it relates to morphine consumption and reward in mice

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT