Insomnia Treatment Drug Lemborexant Rescues Sleep Dysfunction Associated with Methamphetamine Vapor Withdrawal
Location
Culp Center Ballroom
Start Date
4-25-2023 9:00 AM
End Date
4-25-2023 11:00 AM
Poster Number
20
Faculty Sponsor’s Department
Biomedical Sciences
Name of Project's Faculty Sponsor
Brooke Schmeichel
Competition Type
Competitive
Type
Poster Presentation
Project's Category
Neuroscience
Abstract or Artist's Statement
Introduction: In 2021, 2.5 million people aged 12 and older abused the addictive psychostimulant methamphetamine (MA) in the US. MA produces short-lasting euphoria, but also anxiety, erratic behavior, mood disturbance, and abnormal wakefulness. Chronic use of MA can lead to disordered sleep, particularly during withdrawal, and clinical studies have shown that sleep dysfunction is a strong predictor for drug-taking relapse. The neuropeptide hypocretin (HCRT) plays a critical role in the transition to a waking state and also modulates drug reward. Enhanced HCRT signaling in the brain underlies the sleep disorder insomnia and the HCRT-receptor antagonist lemborexant has recently been FDA-approved for treatment of insomnia in humans. Thus, in the current study we characterize sleep dysfunction associated with MA vapor withdrawal and hypothesize that HCRT signaling contributes to negative sleep outcomes.
Methods: Adult male Wistar rats (N =8) were implanted with a telemetry device and electroencephalographic/electromyographic signals were recorded for 24 hours (12:12 hours, light:dark cycle). Data were analyzed prior to MA vapor exposure (baseline), and during withdrawal (after one week of MA vapor abstinence). Rats were administered lemborexant (0, and 30 mg/kg, in a counter-balanced order) during withdrawal at the beginning of the light cycle.
Results: Rats showed a decrease in time spent in rapid eye movement (REM) sleep in the light cycle during withdrawal, and there was a trend for an increase in time spent in REM sleep during the dark cycle, indicating possible REM sleep rebound. There were no changes to non-REM (NREM) sleep or waking in either the light or dark cycle. The number of bouts of REM sleep decreased during the light cycle, and there was no change in average bout duration in REM sleep during withdrawal compared to baseline. The number of bouts of NREM sleep and waking increased during the dark cycle, while the average bout duration decreased during withdrawal compared to baseline, indicating periods of sleep/wake were more fragmented during the dark cycle. In addition, administration of lemborexant restored the amount of time spent in REM sleep and the number of REM sleep bouts during the light cycle.
Conclusions: Overall, these findings show there is a role for HCRT neurotransmission in the observed dysregulated and fragmented sleep of male rats during MA withdrawal. Future research should look at gender differences for sleep dysfunction and MA withdrawal, as well as long-term consequences of MA use.
Insomnia Treatment Drug Lemborexant Rescues Sleep Dysfunction Associated with Methamphetamine Vapor Withdrawal
Culp Center Ballroom
Introduction: In 2021, 2.5 million people aged 12 and older abused the addictive psychostimulant methamphetamine (MA) in the US. MA produces short-lasting euphoria, but also anxiety, erratic behavior, mood disturbance, and abnormal wakefulness. Chronic use of MA can lead to disordered sleep, particularly during withdrawal, and clinical studies have shown that sleep dysfunction is a strong predictor for drug-taking relapse. The neuropeptide hypocretin (HCRT) plays a critical role in the transition to a waking state and also modulates drug reward. Enhanced HCRT signaling in the brain underlies the sleep disorder insomnia and the HCRT-receptor antagonist lemborexant has recently been FDA-approved for treatment of insomnia in humans. Thus, in the current study we characterize sleep dysfunction associated with MA vapor withdrawal and hypothesize that HCRT signaling contributes to negative sleep outcomes.
Methods: Adult male Wistar rats (N =8) were implanted with a telemetry device and electroencephalographic/electromyographic signals were recorded for 24 hours (12:12 hours, light:dark cycle). Data were analyzed prior to MA vapor exposure (baseline), and during withdrawal (after one week of MA vapor abstinence). Rats were administered lemborexant (0, and 30 mg/kg, in a counter-balanced order) during withdrawal at the beginning of the light cycle.
Results: Rats showed a decrease in time spent in rapid eye movement (REM) sleep in the light cycle during withdrawal, and there was a trend for an increase in time spent in REM sleep during the dark cycle, indicating possible REM sleep rebound. There were no changes to non-REM (NREM) sleep or waking in either the light or dark cycle. The number of bouts of REM sleep decreased during the light cycle, and there was no change in average bout duration in REM sleep during withdrawal compared to baseline. The number of bouts of NREM sleep and waking increased during the dark cycle, while the average bout duration decreased during withdrawal compared to baseline, indicating periods of sleep/wake were more fragmented during the dark cycle. In addition, administration of lemborexant restored the amount of time spent in REM sleep and the number of REM sleep bouts during the light cycle.
Conclusions: Overall, these findings show there is a role for HCRT neurotransmission in the observed dysregulated and fragmented sleep of male rats during MA withdrawal. Future research should look at gender differences for sleep dysfunction and MA withdrawal, as well as long-term consequences of MA use.