NON-NMDA RECEPTORS MODULATE RESPIRATORY DRIVE IN FETAL SHEEP

1. Experiments were carried out in unanaesthetized fetal sheep to eval uate the significance of non-N-methyl-D-aspartate (non-NMDA) receptor neurotransmission in the expression of fetal breathing movements. Cath eters placed in the trachea and amniotic fluid and electrodes beneath the parietal bones and in the nuchal muscle were used to monitor breat h amplitude and frequency and fetal behavioural state. 2. Experiments were carried out by instillation of neurotransmitter agonists, antagon ists or receptor modulators into the cerebrospinal fluid (CSF) of the fourth ventricle by means of a chronic catheter introduced through the foramen magnum. 3. The non-NMDA receptor antagonist 6-cyano-7-nitroqu inoxaline-2,3-dione (CNQX) decreased respiratory rate in a dose depend ent manner by lengthening both inspiratory time (II,) and expiratory t ime (T-e). 4. Kainate and lpha-amino-3-hydroxy-5-methylisoxazole-4-pro pionic acid (AMPA) increased breath amplitude. Instillation of the ant agonist 2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f) quinoxaline (NBQX) p rior to administering AMPA resulted in apnoea, which was not overcome by the agonist. 5. Cyclothiazide, which has been shown to prevent dese nsitization of AMPA receptors, caused an increase in both breath ampli tude (152 +/- 73%; mean +/- S.D.; P = 0.004) and frequency (46 +/- 37% ; P = 0.049). 6. These data suggest that glutamate acting at non-NMDA receptors is an essential component for the expression of fetal breath ing movements, and that under resting conditions these non-NMDA recept ors are desensitized following glutamate synaptic release.