Role of non-NMDA glutamate receptors in respiratory control and hyperoxia-induced plasticity in neonatal rats

Abstract

Newborn rats have a biphasic hypoxic ventilatory response (HVR) that typically matures during the second postnatal week, but rats reared in moderate hyperoxia (30-60 % O₂) already exhibit a sustained increase in ventilation during the late-phase of the HVR by 3 days of age (P3). Enhanced glutamatergic neurotransmission through NMDA receptors contributes to both normal maturation of the HVR and hyperoxia-induced developmental plasticity, but the role of non-NMDA glutamate receptors is unclear. To investigate the involvement of non-NMDA glutamate receptors in respiratory control and hyperoxia-induced plasticity, newborn Sprague Dawley rats were exposed to 21 % O₂ (Control) or 60 % O₂ (Hyperoxia) until their HVR was measured by head-body plethysmography at P3-4. Systemic administration of the AMPA/kainate 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 and convection requirement. NBQX also attenuated the HVR measured during the first minute of hypoxia in both treatment groups, but it did not alter the overall shape of the HVR; Hyperoxia rats exhibited a sustained increase in ventilation throughout the entire 15-min exposure to 11 % O₂ regardless of whether they received saline or NBQX injections, while Control rats had a strongly biphasic HVR. Therefore, glutamatergic neurotransmission via non-NMDA glutamate receptors plays an important role in the respiratory control of neonatal rats but not in the respiratory plasticity expressed after chronic postnatal hyperoxia.

Keywords: AMPA receptor; Control of breathing; Development; Hyperoxia; Hypoxic ventilatory response; Kainate receptor.