Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice

Bedard, Madigan L.; Lord, Julia S.; Perez, Patric J.; Bravo, Isabel M.; Teklezghi, Adonay; Tarantino, Lisa M.; Diering, Graham H.; McElligott, Zoé A.

doi:10.1016/j.bbr.2023.114441

Cited by 9 publications

(24 citation statements)

References 60 publications

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“…Nonetheless, during chronic opioid administration, animals are consistently reported to develop behavioural tolerance indicated by a progressive increase in activity across treatment days, in both constant or escalating dose paradigms (Babbini & Davis, 1972;Paul et al, 2021). As has been reported previously in other escalating dose paradigms, all doses in the present study promoted activity, an effect that was more pronounced as the dose increased and the chronic treatment phase progressed (Figure 3a (Khazan & Colasanti, 1972), to the best of our knowledge, these results have not been replicated in mice experiencing withdrawal from chronic opioid treatment (Bedard et al, 2023;Eacret et al, 2022;Gamble et al, 2022). Our results in the current study in mice (Figures 4b',c' and 5b',c') are thus consistent with effects on sleep/wake reported in other mammals.…”

Section: Morphine Acutely Impacts Activity and Body Weightsupporting

confidence: 82%

Biological sex influences sleep phenotype in mice experiencing spontaneous opioid withdrawal

Tisdale,

Sun,

Park

et al. 2023

Journal of Sleep Research

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SummaryAversive symptoms, including insomnia experienced during opioid withdrawal, are a major drive to relapse; however, withdrawal‐associated sleep symptomatology has been little explored in preclinical models. We describe here a model of opioid withdrawal in mice that resembles the sleep phenotype characteristic of withdrawal in humans. Male and female C57BL/6 mice were instrumented with telemeters to record electroencephalogram, electromyogram, activity and subcutaneous temperature. All mice received two treatments separated by a 16‐day washout period: (1) saline (volume: 10 ml kg−1); or (2) ascending doses of morphine (5, 10, 20, 40 and 80 mg kg−1; volume: 10 ml kg−1) for 5 days at Zeitgeber time 1 and Zeitgeber time 13. Recordings for the first 71 hr after treatment discontinuation (withdrawal days 1–3) and for 24 hr on withdrawal days 5 and 7 were scored for sleep/wake state, and sleep architecture and electroencephalogram spectral data were analysed. Morphine was acutely wake‐ and activity‐promoting, and non‐rapid eye movement and rapid eye movement sleep were increased during the dark phase on withdrawal day 2 in both sexes. While non‐rapid eye movement delta power (0.5–4.0 Hz), a measure of sleep intensity, was reduced during the light phase on withdrawal day 1 and the dark phase on withdrawal day 2 in both sexes, female mice also exhibited changes in the duration and the number of bouts of sleep/wake states. These observations of fragmented sleep on withdrawal days 1–3 suggest poorer sleep consolidation and a more pronounced withdrawal‐associated sleep phenotype in female than in male mice. These data may indicate a greater sensitivity to morphine, a more distinct aversive sleep phenotype and/or a faster escalation to dependence in female mice.

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Section: Morphine Acutely Impacts Activity and Body Weightsupporting

confidence: 82%

Biological sex influences sleep phenotype in mice experiencing spontaneous opioid withdrawal

Tisdale,

Sun,

Park

et al. 2023

Journal of Sleep Research

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“…This could be done by including tests such as startle response or digging, and other home cage behaviors assessed by deep learning methods to measure affective behavior . Sleep disruptions have also proven to illuminate sex differences in withdrawal experiences . Ultrasonic vocalizations have also been used to study withdrawal, particularly in neonates, and provide a useful measure of affective symptoms .…”

Section: Modeling Opioid Withdrawalmentioning

confidence: 99%

“…continued proven to illuminate sex differences in withdrawal experiences. 65 Ultrasonic vocalizations have also been used to study withdrawal, particularly in neonates, and provide a useful measure of affective symptoms. 80 There are many other options available, and researchers should carefully determine the best ways to assess withdrawal.…”

Section: Withdrawal Behavior Scoringmentioning

confidence: 99%

“…Our recent study shows different effects of spontaneous and NPW on sleep in mice during and following a 3-day paradigm, indicating that the type of withdrawal can alter recovery from morphine exposure. 65 Other studies from the Rothwell lab showed that continuous morphine exposure resulted in tolerance to psychomotor effects while intermittent (daily injections, akin to spontaneous withdrawal) and interrupted (continuous minipump with NPW) resulted in sensitization to the psychomotor effects and that these effects were accompanied by downstream signaling changes. 76,77 Furthermore, more studies are needed to examine NPW following a single opioid exposure (sometimes called acute dependence 72 ) to shed light on the effects of fentanyl poisonings in those who are not opioid dependent.…”

Section: Modeling Opioid Withdrawalmentioning

confidence: 99%

“…Additionally, it provides a different dimension of dependence. For example, our lab uses a sensitizing repeated withdrawal model to a relatively low but rewarding dose of morphine. − This allows us to examine the impact of withdrawal severity (which escalates across our treatment regimen) as opposed to increased drug exposure. It has also allowed us to examine how the experience of exacerbated withdrawal leads to long-lasting (months) behavioral plasticity .…”

Section: Modeling Opioid Withdrawalmentioning

confidence: 99%

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All Hands on Deck: We Need Multiple Approaches To Uncover the Neuroscience behind the Opioid Overdose Crisis

Bedard,

Nowlan,

Martin del Campo

et al. 2023

ACS Chem. Neurosci.

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Opioid use disorder (OUD) affects millions of people throughout the United States, yet there are only three Food and Drug Administration-approved pharmacological treatments. Though these treatments have been shown to be effective, the number of overdose deaths continues to rise. The increase of fentanyl, fentanyl analogs, and adulterants in the illicit drug supply has further complicated treatment strategies. Preclinical researchers strive to model OUD to better understand this complicated disorder, and this research is a critical enabler for the development of novel treatments. As a result, there are many different preclinical models of OUD. Often, researchers form strong opinions on what they believe to be the "best" model to mimic the human condition. Here, we argue that researchers should be supportive of multiple models to promote new perspectives and discoveries and always consider the trends in human opioid use when designing preclinical studies. We describe the benefits of contingent and noncontingent models as well as models of opioid withdrawal and how each of these can help illuminate different components of OUD.

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Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism

Bedard,

Huang,

Murray

et al. 2024

Addiction Neuroscience

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Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice

Cited by 9 publications

References 60 publications

Biological sex influences sleep phenotype in mice experiencing spontaneous opioid withdrawal

Biological sex influences sleep phenotype in mice experiencing spontaneous opioid withdrawal

All Hands on Deck: We Need Multiple Approaches To Uncover the Neuroscience behind the Opioid Overdose Crisis

Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism

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