AMPA glutamate receptors and respiratory control in the developing rat: anatomic and pharmacological aspects

The developmental role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropion ate (AMPA) glutamate receptors in respiratory regulation remains undefined. To study this issue, minute ventilation ((V) over dot(E)) was measured in 5-, 10-, and 15-day-old intact freely behaving rat pups using whole body pl ethysmography during room air (RA), hypercapnic (5% CO2), and hypoxic (10% O-2) conditions, both before and after administration of the non-N-methyl-D -aspartate (NMDA) receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxob enzo[f]quinoxaline-7-sulfonamide disodium (NBQX; 10 mg/kg ip). In all age g roups, (V) over dot(E) during RA was unaffected by NBQX, despite reductions in breathing frequency (f) induced by increases in both inspiratory and ex piratory duration. During hypoxia and hypercapnia, (V) over dot(E) increase s were similar in both NBQX and control conditions in all age groups. Howev er, tidal volume was greater and flower after NBQX. To determine if AMPA re ceptor-positive neurons are recruited during hypoxia, immunostaining for AM PA receptor (GluR2/3) and c-fos colabeling was performed in caudal brain st em sections after exposing rat pups at postnatal ages 2, 5, 10, and 20 days , and adult rats to room air or 10% O-2 for 3 h. GluR2/3 expression increas ed with postnatal age in the nucleus of the solitary tract (NTS) and hypogl ossal nucleus, whereas a biphasic pattern emerged for the nucleus ambiguus (NA). c-fos expression was enhanced by hypoxia at all postnatal ages in the NTS and NA and also demonstrated a clear maturational pattern. However, co localization of GluR2/3 and c-fos was not affected by hypoxia. We conclude that AMPA glutamate receptor expression in the caudal brain stem is develop mentally regulated. Furthermore, the role of non-NMDA receptors in respirat ory control of conscious neonatal rats appears to be limited to modest, alb eit significant, regulation of breathing pattern.