Solriamfetol enhances wakefulness and improves cognition and anxiety in a murine model of OSA

Background: Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH). Excessive daytime sleepiness (EDS) is a common consequence of OSA and is associated with cognitive deficits and anxiety. Modafinil (MOD) and Solriamfetol (SOL) are potent wake-promoting agents clinically used to improve wakefulness in OSA patients with EDS. Methods: Male C57Bl/6J mice were exposed to either IH or room air (RA) controls during the light phase for 16 weeks. Both groups were then randomly assigned to receive once-daily intraperitoneal injections of SOL (200 mg/kg), MOD (200 mg/kg) or vehicle (VEH) for 9 days while continuing IH exposures. Sleep/ wake activity was assessed during the dark (active) phase. Novel object recognition (NOR), elevated-plus maze test (EPMT), and forced swim test (FST) were performed before and after drug treatment. Results: IH exposure increased dark phase sleep percentage and reduced wake bouts lengths and induced cognitive deficits and anxiogenic effects. Both SOL and MOD treatments decreased sleep pro-pensity under IH conditions, but only SOL promoted improvements in NOR performance (explicit memory) and reduced anxiety-like behaviors. Conclusion: Chronic IH, a hallmark feature of OSA, induces EDS in young adult mice that is ameliorated by both SOL and MOD. SOL, but not MOD, significantly improves IH-induced cognitive deficits and promotes anxiolytic effects. Thus, SOL could potentially benefit OSA patients beyond EDS management. (c) 2023 Elsevier B.V. All rights reserved.