Non-NMDA receptors in the nucleus of the solitary tract play a role in ventilatory acclimatization to hypoxia in rats

Ventilatory acclimatization to hypoxia (VAH) increases both (1) the hypoxic ventilatory response (HVR) to acute decreases in arterial PO₂, and (2) normoxic ventilatory drive when inspired O₂ is returned to normal. Previous studies have shown that N-methyl-D-aspartate (NMDA) receptors in the nucleus of the solitary tract (NTS) are involved in the acute HVR of awake rats. We hypothesized that non-NMDA receptors in the NTS are necessary for the complete manifestation of the VAH. To test this, male Sprague-Dawley rats were randomly divided into two groups: (1) normoxic sea level control (N, n = 13) and (2) chronically hypoxic rats (CH, n = 11) acclimatized in a hypobaric chamber (PIO₂ = 70 Torr) for 7 days. We microinjected artificial cerebrospinal fluid (aCSF) as a sham, and a non-NMDA receptor antagonist into the NTS (0.02 mmol NBQX in 50 nL, bilaterally) through a stereotaxically placed guide cannula. We used barometric pressure plethysmography to measure ventilation during acute hypoxia (10% O₂), normoxia (21% O₂) and acute hypercapnia (7% CO₂). We microinjected AMPA into the same location in the NTS of a subset of the same animals to confirm effectiveness of the NBQX. Microinjection sites were identified by colloidal gold or Evan's blue microinjections after the experiment. Non-NMDA receptor blockade with NBQX significantly (P<0.05) decreased the normoxic ventilatory drive after chronic hypoxia, but not in the normoxic control rats. In addition, non-NMDA receptor blockade depressed ventilation for both normoxic and chronically hypoxic rats acutely breathing hypoxic and hypercapnic gas. The ventilatory response to NBQX resulted primarily from significant effects on respiratory frequency, but not tidal volume. Hence, non-NMDA receptors in the NTS play a role in VAH, and are important for ventilatory drive during chronic and acute hypoxi