NMDA RECEPTORS ARE INVOLVED AT THE VENTROLATERAL NUCLEUS-TRACTUS-SOLITARII FOR TERMINATION OF INSPIRATION

The purpose of the present study was to determine whether blockade of excitatory amino acid receptors at the ventrolateral nucleus of the tr actus solitarius would influence respiratory activity. This was done b y microinjecting excitatory amino acid receptor antagonists into the v entrolateral nucleus of the tractus solitarius of alpha-chloralose-ane sthetized animals while monitoring respiratory activity using a Fleisc h pneumotachograph and arterial blood pressure and heart rate. Bilater al microinjection of the NMDA receptor antagonist, 3-[(R)-carboxypiper azin-4-yl]-propyl-1-phosphomic acid (CPP), 5.62 nmol per side, produce d an increase in inspiratory duration (+4+/-1.6 s, n=8) which progress ed to an apneustic pattern of breathing. Similar results were obtained with CPP microinjected into the ventrolateral nucleus of the tractus solitarius of three vagotomized animals. Bilateral microinjection of a second NMDA receptor antagonist, 2-amino-7-phosphono-heptanoic acid ( AP7), 562 nmol per side, produced qualitatively similar effects on res piration as seen with CPP. In contrast, blockade of non-NMDA receptors with 6-cyano-7-nitroquinoxaline-2,3-dione (CNXQ), 0.125 nmol per side , had very little effect on respiration. Activation of NMDA receptors at the ventrolateral nucleus of the tractus solitarius with bilateral microinjection of NMDA, 39 pmol, produced a large increase in expirato ry duration (+11+/-3 s, n=8), and apnea during the expiratory phase of the respiratory cycle in half of the animals studied, Similar results were obtained with ha-amino-3-hydroxy-5-methyl-4-isoxazol-proprionate (AMPA). These results indicate that an endogenous excitatory amino ac id released at the ventrolateral nucleus of the tractus solitarius and acting at the NMDA receptor, plays a significant role in respiratory timing.