006 The effect of sodium oxybate on cataplexy in orexin knockout mice

Abstract Introduction Narcolepsy is a neurological disorder that characterized by the loss of orexin neurons in lateral hypothalamus. Cataplexy symptom narcolepsy and identified sudden muscle tone during wakefulness. abruptly interrupts day-to-day activities, makes activities like driving dangerous potentially fatal. It hypothesized cataplexy occurs due to intrusion REM sleep atonia has been demonstrated GABAergic mechanism responsible for silencing circuit preventing from occurring Sodium oxybate (SXB), low affinity agonist GABAB receptors, currently an approved treatment narcolepsy; however, its action brain remains unknown. Here, we investigate hypothesis SXB prevents through mediated suppressing circuit. Methods We intraperitoneally (IP) injected orexin-/- mice with one five treatments; either Lactated Ringers Solution, at 50, 100, or 200 mg/kg, Phaclophen 10 mg/kg followed 100 mg/kg. was assessed video recordings. gathered analyzed data three distinct chronological time points (i.e, baseline, after consecutive weeks daily dosing treatment, week no treatment). These experiments were designed conducted determine whether; 1) reduces cataplexy, 2) cessation administration effect on 3) mechanism. Results first confirmed used indeed using immunohistochemical analysis show orexin-a expressing located Then, determined that: compared matched controls (unpaired t-test, p=0.0027, n=18); When stopped administering IP injections, levels increased towards control (paired p=0.0024, it unclear if SXB’s solely Conclusion Our findings demonstrate effectively mice. Support (if any) This research funded Jazz Pharmaceuticals