Though respiratory regulation in newborns has many similarities with adults, quantitative and qualitative differences exist. It is possible that these developmental differences account for the pronounced susceptibility of newborn infants to have prolonged spontaneous apnea. The present studies are based on the hypothesis that central neural mechanisms are more important in respiratory regulation than traditionally recognized. The long-range objective is to develop an understanding of central neural mechanisms which destabilize respiratory drive. The specific objective of this study is to characterize the influence of central neural mechanisms on the respiratory response to hypoxia and on reinitiation of breathing following onset of apnea. An experimental animal model has been developed which eliminates the effect of negative chemical feedback that usually follows a change in ventilation but which allows quantitation of respiratory output by measuring phrenic nerve activity. Two studies are proposed which utilize this model. One utilizes stimulation of th carotid sinus nerve to stimulate hypoxia and the other utilizes stimulation of the superior laryngeal nerve to induce central apnea. Our preliminary results suggest that stimulation of either nerve activates neural mechanisms which serve to inhibit central respiratory drive for a long period. In addition, these inhibition mechanisms may also affect neural drive to upper airway muscles which are important in maintaining airway patency. It is likely that these inhibitory mechanisms are mediated by neurotransmitters. Imbalance of the transmitters that stimulate and those that depress respiration may occur during hypoxia. Therefore, the second objective of this study is to identify changes in neurotransmitter levels and metabolism caused by hypoxia. Neurochemical determinations of biogenic amine and endorphin metabolism in brainstem respiratory nuclei of newborn rabbits will be made in hypoxic and control rabbit pups. The interaction of central excitatory and inhibitory influences on the respiratory centers may have important implications for premature newborns with apnea as well as older infants at risk for the sudden-infant-death syndrome and possible adults with obstructive sleep apnea.