The influence of NMDA receptor-mediated processes on breathing pattern in ground squirrels.
The effects of blockade of N-methyl-D-aspartate (NMDA) type glutamate receptors by a non-competitive antagonist (MK-801) on cortical arousal, breathing pattern and ventilatory responses to hypoxia (10% O2 in N2) and hypercapnia (5% CO2 in air) were assessed in anesthetized (urethane) and unanesthetized golden-mantled ground squirrels (Spermophilus lateralis). Intra-cerebroventricular administration of MK-801 did not alter ventilation during wakefulness, although it did alter the pattern (breathing frequency and tidal volume components) of the hypercapnic ventilatory response, and suppressed the ventilatory response to hypoxia. Animals did not sleep following treatment with MK-801, and intravenous administration of MK-801 prevented expression of the sleep-like state normally observed in anesthetized animals. In anesthetized animals MK-801 elevated breathing frequency to levels observed without anesthesia, and suppressed the hypoxic ventilatory response. These data suggest that NMDA-type glutamatergic receptor-mediated processes influence cortical arousal and facilitate depression of breathing frequency during anesthesia and the hypoxic ventilatory response. Such processes are not essential for the hypercapnic ventilatory response.
Department of Zoology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada. michael.b.harris@dartmouth.edu
M B
MB
Harris
W K
WK
Milsom
D000208:Acute Disease; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004569:Electroencephalography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D012589:Sciuridae / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate