Role of Non-NMDA Glutamate Receptors in Respiratory Control and Hyperoxia-induced Plasticity in Neonatal Rats

Newborn rats have a biphasic hypoxic ventilatory response (HVR) that typically matures during the second postnatal week. In contrast, neonatal rats reared in moderate hyperoxia exhibit a sustained increase in ventilation during the late-phase of the HVR by 3 days of age (P3), and this earlier-than-expected transition from a biphasic HVR to a sustained HVR is partially mediated through NMDA receptors (Bavis et al., Respir Physiol Neurobiol 191: 84-94, 2014). To determine whether non-NMDA glutamate receptors also contribute to this respiratory plasticity, newborn Sprague Dawley rats were exposed to 21% O 2 (Control) or 60% O 2 (Hyperoxia) until their HVR were measured by head-body plethysmography at P3-4. Systemic administration of the non-NMDA glutamate receptor antagonist NBQX (12.5 mg kg -1 , i.p.) caused rats from both treatment groups to adopt a slower, deeper breathing pattern with a modest reduction in baseline minute ventilation. As a result, baseline O 2 convection requirement was approximately 13% lower after NBQX. NBQX also attenuated the HVR measured during the first minute of acute hypoxia in both treatment groups, but it did not alter the overall shape of the HVR. Specifically, Hyperoxia rats exhibited a sustained increase in ventilation throughout the entire 15-minute exposure to 11% O 2 regardless of whether they received saline or NBQX injections, while Control rats exhibited a strongly biphasic HVR. Therefore, non-NMDA glutamate receptors do not appear to contribute to the expression of respiratory plasticity after chronic postnatal hyperoxia. However, contrary to prior reports, non-NMDA glutamate receptors have significant effects on normoxic ventilation and the acute HVR in neonatal rats. Supported by the Department of Biology at Bates College. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.