MATURATION OF ANOXIA-INDUCED GASPING IN THE RAT - POTENTIAL ROLE FOR N-METHYL-D-ASPARTATE GLUTAMATE RECEPTORS

After anoxia-induced apnea, gasping remains the last operative mechani sm for survival. In developing rats, the gasping response to anoxia ex hibits triphasic characteristics. Because anoxia is associated with en hanced release of glutamate, we hypothesized that N-methyl-D-aspartate (NMDA) glutamate receptors may underlie components of the gasping res ponse. 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% Nz in a whole body p lethysmograph, 30 min after intraperitoneal administration of MK801 [( +)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d-]cyclohepten-5,10-imine hydr ogen 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 p ostnatal 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 w as 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, altho ugh overall gasping duration was prolonged, the triphasic gasping patt ern seen in matched controls was also present. We conclude that NMDA g lutamate receptors mediate particular phasic components of the gasping response during early postnatal life but not at later stages of devel opment. We speculate that developmental changes occur in both function and expression of NMDA and other neurotransmitters within brainstem r egions underlying the neural substrate for gasp generation.