Preclinical Evidence Supporting the Repurposing of Suvorexant (Belsomra™) to Manage Sleep Disturbances During Initial Cocaine Abstinence

• Published in: Drug and alcohol dependence Vol. 260; p. 109959
• Main Authors: Gyawali, Utsav, Merai, Shuchi, Paladino, Morgan S., James, Morgan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.07.2024
• ISSN: 0376-8716
• DOI: 10.1016/j.drugalcdep.2023.109959

Select Drug Category Stimulants Topic Treatment Abstract Detail Preclinical - In Vivo Abstract Category Original Research A recent study reported that the sleep medication suvorexant (Belsomra™), a dual orexin receptor antagonist, improves sleep and withdrawal outcomes in persons with opioid use disorder during a buprenorphine/naloxone taper. The aim of this study was to test if suvorexant might have similar efficacy in normalizing sleep disturbances during initial cocaine abstinence in rats. In one set of studies, we induced a conditioned place preference (CPP) to non-contingent cocaine injections (10mg/kg) in male Long Evans rats (n=9). CPP was extinguished across 5 daily extinction sessions. In a second set of experiments, female Sprague Dawley rats (n=9) were trained to self-administer cocaine on an intermittent access schedule for 14d before undergoing extinction training. In both groups, rats received suvorexant (0, 30mg/kg, p.o) immediately prior to the onset of the inactive period during extinction. Sleep was monitored during cocaine exposure and the suvorexant treatment period using electroencephalogram (EEG) and electromyogram (EMG) recordings. All data were analyzed using mixed-model ANOVA. Cocaine abstinence was associated with increased time spent in active wake, reduced time spent in rapid eye movement (REM) and non-REM sleep, and increased sleep fragmentation (all p’s<0.05, vs. baseline). Suvorexant normalized sleep outcomes (active wake, REM, non-REM sleep: p’s<0.01; fragmentation: p<0.05) and facilitated extinction of both CPP and lever responding (p’s<0.05). Suvorexant normalizes sleep disturbances associated with initial cocaine abstinence and facilitates the extinction of cocaine seeking behaviors. These data support the potential repurposing of suvorexant for the management of cocaine use disorder.