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 propensity 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.