We evaluated the hypothesis that N-methyl-D-aspartate (NMDA) receptors
in the rostral pens mediate the off-switch of inspiration in the adul
t rat. Experiments were performed on decerebrate, vagotomized, paralyz
ed and ventilated animals. Activity of phrenic nerve was recorded. Sma
ll volumes (10 nl) of NMDA antagonists, MK-801 and AP-5, or non-NMDA a
ntagonists, CNQX and DNQX, were injected into the rostral pens. We fou
nd that injections of MK-801 reversibly increased the duration of neur
al inspiration (TI), and the increase was dose-dependent. Injections o
f AP-5 also increased TI. Injections of the DNQX and CNQX in these sam
e loci resulted in no significant changes in the duration of neural in
spiration, expiration or peak phrenic activity (PNA). However, injecti
ons of kainic acid (KA, 4.7 mM) in the loci increased TI and decreased
PNA. We conclude that neurons regulating the off-switch mechanism are
located in the rostral pens. Further, the binding of NMDA receptors i
n the rostral pens is involved in this off-switch mechanism.