Physiology Commons^™

Cholinergic Modulation Of Narcoleptic Attacks In Double Orexin Receptor Knockout Mice, Mike Kalogiannis, Emily Hsu, Jon Willie, Richard Chemelli, Yaz Kisanuki, Masashi Yanagisawa, Christopher S. Leonard

NYMC Faculty Publications

To investigate how cholinergic systems regulate aspects of the sleep disorder narcolepsy, we video-monitored mice lacking both orexin (hypocretin) receptors (double knockout; DKO mice) while pharmacologically altering cholinergic transmission. Spontaneous behavioral arrests in DKO mice were highly similar to those reported in orexin-deficient mice and were never observed in wild-type (WT) mice. A survival analysis revealed that arrest lifetimes were exponentially distributed indicating that random, Markovian processes determine arrest lifetime. Low doses (0.01, 0.03 mg/kg, i.p.), but not a high dose (0.08 mg/kg, i.p.) of the cholinesterase inhibitor physostigmine increased the number of arrests but did not alter arrest lifetimes. …