RAT RETROTRAPEZOID NUCLEUS IONOTROPIC AND METABOTROPIC GLUTAMATE RECEPTORS AND THE CONTROL OF BREATHING

We injected 10 nl (unilateral) of glutamate receptor antagonists or ag onists into the region of the retrotrapezoid nucleus and measured the phrenic nerve and blood pressure responses. The rats were chloralose-u rethan anesthetized, paralyzed, vagotomized, and ventilated, and each injection location was verified anatomically. Integrated phrenic ampli tude was most reliably affects. The N-methyl-D-aspartic acid (NMDA) an tagonists 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxa line-2,3-dione (which effects both NMDA and non-NMDA receptors) both d ecreased baseline eucapnic phrenic amplitude and the CO2 response. Glu tamate increased phrenic amplitude in a dose-dependent manner, an effe ct blocked by prior injection of the NMDA and non-NMDA antagonists at the same site. The response duration depended on the duration of the g lutamate injection: responses to 3-s injections lasted a few minutes, and responses to 60-s injections lasted for >30 min. The long-lasting effect was reproduced by injection of the metabotropic agonist 1(S), 3 (R)-aminocyclopentanedicarboxylic acid at 0.01-0.02 times the glutamat e dose. We conclude that the rat retrotrapezoid nucleus has an endogen ous source of glutamate that maintains eucapnic phrenic output and all ows expression of the CO2 response. NMDA and possibly non-NMDA recepto rs are involved. Their stimulation increases phrenic output via ionotr opic and metabotropic receptor processes with the latter resulting in long-lasting phrenic stimulation.