title: The competitive NMDA receptor antagonist CPPene stimulates NREM sleep and eating in rats.
abstract: Systemic administration of noncompetitive NMDA receptor antagonists, such as MK-801, produces a period of intoxication followed by non- rapid eye movement (NREM) sleep with greatly elevated delta EEG activity. We have hypothesized that the delayed NREM delta EEG increase is a homeostatic response to the immediate elevated limbic metabolism that these drugs produce. Here we test this hypothesis by examining the sleep and EEG effects of CPPene, a competitive NMDA antagonist that does not elevate limbic metabolism. We recorded EEG in seven rats following mid-dark period systemic injections of saline and three doses of CPPene. CPPene did not produce the delayed NREM delta increase. Instead, CPPene increased eating time and dose dependently increased NREM sleep duration shortly after injection. These differences in sleep EEG response to a competitive versus the noncompetitive NMDA antagonists are consistent with the possibility that the increased NREM delta following noncompetitive antagonists is a homeostatic response to increased limbic metabolism.
authors.affiliation: Veterans Administration Northern California Health Care System, VA/UCD Sleep Lab TB148, Department of Psychiatry, University of California, Davis, CA 95616, USA. igcampbell@ucdavis.edu
authors.forename: Ian Glenn
authors.initials: IG
authors.lastname: Campbell
authors.forename: Lorell Marie
authors.initials: LM
authors.lastname: Gustafson
authors.forename: Irwin
authors.initials: I
authors.lastname: Feinberg
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494