Endocannabinoid agonist 2-arachidonoylglycerol differentially alters diurnal activity and sleep during fentanyl withdrawal in male and female mice.
Pharmacol Biochem Behav
; 240: 173791, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38761993
ABSTRACT
Fentanyl has become the leading driver of opioid overdoses in the United States. Cessation of opioid use represents a challenge as the experience of withdrawal drives subsequent relapse. One of the most prominent withdrawal symptoms that can contribute to opioid craving and vulnerability to relapse is sleep disruption. The endocannabinoid agonist, 2-Arachidonoylglycerol (2-AG), may promote sleep and reduce withdrawal severity; however, the effects of 2-AG on sleep disruption during opioid withdrawal have yet to be assessed. Here, we investigated the effects of 2-AG administration on sleep-wake behavior and diurnal activity in mice during withdrawal from fentanyl. Sleep-wake activity measured via actigraphy was continuously recorded before and after chronic fentanyl administration in both male and female C57BL/6J mice. Immediately following cessation of fentanyl administration, 2-AG was administered intraperitoneally to investigate the impact of endocannabinoid agonism on opioid-induced sleep disruption. We found that female mice maintained higher activity levels in response to chronic fentanyl than male mice. Furthermore, fentanyl administration increased wake and decreased sleep during the light period and inversely increased sleep and decreased wake in the dark period in both sexes. 2-AG treatment increased arousal and decreased sleep in both sexes during first 24-h of withdrawal. On withdrawal day 2, only females showed increased wakefulness with no changes in males, but by withdrawal day 3 male mice displayed decreased rapid-eye movement sleep during the dark period with no changes in female mice. Overall, repeated administration of fentanyl altered sleep and diurnal activity and administration of the endocannabinoid agonist, 2-AG, had sex-specific effects on fentanyl-induced sleep and diurnal changes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sueño
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Síndrome de Abstinencia a Sustancias
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Ácidos Araquidónicos
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Fentanilo
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Ritmo Circadiano
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Endocannabinoides
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Glicéridos
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Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
Pharmacol Biochem Behav
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos