Abstract
After anoxia-induced apnea, gasping remains the last operative mechanism for survival. In developing rats, the gasping response to anoxia exhibits triphasic characteristics. Because anoxia is associated with enhanced release of glutamate, we hypothesized that N-methyl-D-aspartate (NMDA) glutamate receptors may underlie components of the gasping response. Rat pups aged 2 d (n = 50), 5 d (n = 43), 10 d (n = 42), and 15 d (n = 45) underwent anoxic challenges with 100% N2 in a whole body plethysmograph, 30 min after intraperitoneal administration of MK801[(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d-]cyclohepten-5,10-imine hydrogen maleate; dizocilpine] (3 mg/kg), a noncompetitive NMDA glutamate receptor channel antagonist, or normal saline. In control pups, after primary apnea onset, a triphasic gasping pattern was apparent at all postnatal ages and included two distinct types of gasps (I and II). In 2- and 5-d MK801-treated animals, phase 1 and type I gasps were absent, leading to marked prolongations of the gasp latency and phase 2, the latter displaying type II gasps only. In addition, phase 3 duration was also prolonged with increased type II gasp frequencies. In contrast, in some 10-d-old (40%) and in all 15-d-old MK801-treated pups, although overall gasping duration was prolonged, the triphasic gasping pattern seen in matched controls was also present. We conclude that NMDA glutamate receptors mediate particular phasic components of the gasping response during early postnatal life but not at later stages of development. We speculate that developmental changes occur in both function and expression of NMDA and other neurotransmitters within brainstem regions underlying the neural substrate for gasp generation.
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Abbreviations
- GABA:
-
γ-aminobutyric acid
- GAD:
-
glutamic acid decarboxylase
- LTF:
-
lateral tegmental field of the medulla
- MK801 :
-
(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate dizocilpine
- NMDA:
-
N-methyl-D-aspartate glutamate
- NO:
-
nitric oxide
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Supported in part by a grant from the National Institute of Child Health and Development, HD-01072, and by a Bureau of Maternal and Child Health Training Grant MCJ-229163. D.G. is the recipient of a Career Development Award from the American Lung Association.
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Gozal, D., Torres, J. Maturation of Anoxia-Induced Gasping in the Rat: Potential Role forN-Methyl-D-Aspartate Glutamate Receptors. Pediatr Res 42, 872–877 (1997). https://doi.org/10.1203/00006450-199712000-00025
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DOI: https://doi.org/10.1203/00006450-199712000-00025
