INVOLVEMENT OF NMDA RECEPTORS IN THE RESPIRATORY PHASE-TRANSITION IS DIFFERENT IN THE ADULT GUINEA-PIG IN-VIVO AND IN THE ISOLATED BRAIN-STEM PREPARATION

1. We investigated the involvement of N-methyl-D-aspartate (NMDA) rece ptors in the respiratory pattern in an in vitro preparation of adult b rain stem compared with in vivo conditions in the guinea pig. 2. In vi vo, combining administration of the NMDA channel blocker dizocilpine ( MK-801) (3 mg/kg) with a surgical section of the vagus nerves induced an apneustic type of respiration characterized by long inspiratory ''h olds,'' as has been shown in other species. The same effect was observ ed in hypothermic animals (30 degrees C). 3. The isolated in vitro bra in stems from these apneustic animals did not present a prolonged insp iratory phase. A second dose of dizocilpine (100 mu M) perfused vascul arly did not induce apneusis, even after increasing brain stem tempera ture to 35.5 degrees C. 4. In another group of isolated brain stems of adult guinea pigs anesthetized with pentobarbital sodium before decap itation, we perfused dizocilpine and NMDA through the basilar artery. The duration of periodic inspiratory motor activity recorded from the hypoglossal nerve was unaffected by dizocilpine (1-100 mu M) or the co mpetitive NMDA antagonist D- or DL-2-amino-5-phosphono-pentanoic acid (100 mu M and 1 mM), although respiratory frequency decreased. The inc rease in respiratory activity produced by vascularly perfused NMDA (25 -100 mu M) was blocked by dizocilpine(100 mu M). 5. We conclude that t he central mechanism of inspiratory termination in the vagotomized adu lt guinea pig requires the activation of NMDA receptors in vivo but no t in vitro. This difference is not due to the hypothermic environment in vitro. possible mechanisms for phase switching in vitro are discuss ed.