Microdialysis of a NK1R Antagonist into the Ventral Medulla Does Not Affect Breathing Frequency
Federation of the American Society of Experimental Biology
Previous studies in vivo have found an excitatory effect on breathing frequency (f) of microdialysis (MD) of Atropine into regions of the ventral medulla within the vicinity of the pre-Bötzinger Complex (pre-BötC) (FASEB J, 25: 1074.1, 2011). The increase in f was associated with increases in serotonin, substance P (SP), and glycine. These findings suggest that disrupting transmission in one neuromodulator system leads to compensatory changes in other neuromodulators. To determine the effect on breathing of blocking SP neurotransmission, the neurokinin-1 receptor antagonist, Spantide (SPA), was unilaterally microdialyzed in one of two doses (133.5 uM or 267 uM) into sites in the ventral medulla in or near the preBötC of intact goats. Minute ventilation, f, and tidal volume were continuously monitored. Preliminary data show that SPA had minimal effects on these parameters at the lower dose, and suggest that this level of receptor blockade is not enough to stimulate compensatory mechanisms that appreciably affect breathing. However, one of two goats that received both doses of SPA had a dose-dependent increase in breathing frequency with MD of SPA. This finding suggests that blockade of peptidergic neurotransmission at a currently unknown threshold level may also trigger compensatory changes in neurochemicals that stimulate breathing.