Naltrexone blocks the sleep-disrupting effects of methamphetamine in male rhesus monkeys.

Abstract

Methamphetamine has garnered increasing attention due to its escalating recreational use resulting in significant morbidity and mortality. Methamphetamine also significantly alters sleep quality, a finding that has been observed in both human and non-human primates. Naltrexone, an opioid receptor antagonist used in the treatment of opioid and alcohol use disorder, has shown promise as a treatment for methamphetamine use disorder. However, the potential benefits of naltrexone with regards to ameliorating sleep disturbances associated with methamphetamine use are unknown. The aim of the present study was to investigate the acute effects of evening naltrexone administration on the acute sleep-disrupting effects of methamphetamine. Adult male rhesus macaques (N = 4) were fitted with primate collars to which actigraphy monitors were attached. Vehicle or naltrexone (0.03, 0.1, and 0.3mg/kg, i.m.) were administered in the evening (ZT10.5, 1.5h before "lights off") following a morning (ZT4, 4h after "lights on") administration of methamphetamine (0.3mg/kg, i.m.). Our findings replicate previous studies showing that methamphetamine significantly impairs sleep-associated measures in male rhesus monkeys, increasing actigraphy-based measures of sleep latency and wake time after sleep onset (WASO), and decreasing sleep efficiency. Evening treatment with naltrexone dose-dependently improved methamphetamine-induced sleep impairment, with the highest dose significantly improving actigraphy-based measures of sleep latency, sleep efficiency, and WASO. These results suggest that naltrexone may be beneficial in the treatment of methamphetamine use disorder through amelioration of sleep disturbances observed with methamphetamine use.