Ventilatory and Neurochemical Effects of Microdialysis of a µ‐opioid Receptor Agonist (DAMGO) into the Region of the Ventral Respiratory Column in Awake Goats

Abstract

Prior studies (J.appl Phisiol. 114, 694‐647, 2012., Respir Phisiol 205: 7‐15 2014.) have shown that dialysis of antagonists of excitatory neuromodulator receptors in the ventral respiratory column (VRC) resulted in changes in the release of other excitatory neuromodulators with no net change in ventilation. In the present study, we tested the hypothesis that agonists of inhibitory receptors in the VRC will also increase excitatory neuromodulator release by dialyzing DAMGO ([D‐Ala2, N‐MePhe4, Gly‐ol]‐enkephalin), a µ‐opioid receptor agonist, in chronically cannulated awake goats. In five goats we dialyzed mock cerebral spinal fluid (mCSF) with or without DAMGO (10, 50, or 100µM concentrations). Dialysis of 100µM DAMGO resulted in a decrease in tidal volume which was followed by an increase in frequency to maintain ventilation. The concentrations of serotonin, substance P, GABA and glycine in the effluent mCSF were not altered by DAMGO dialysis. We conclude that increased inhibition of VRC respiratory neurons is not compensated for by the same mechanism as during decreased excitation. This work was funded by the National Heart, Lung, and Blood Institute grants HL‐25739, HL‐112996, HL‐007852, and by the Department of Veterans Affairs.