title: Combined unilateral blockade of cholinergic, peptidergic, and serotonergic receptors in the ventral respiratory column does not affect breathing in awake or sleeping goats.
abstract: Previous work in intact awake and sleeping goats has found that unilateral blockade of excitatory inputs in the ventral respiratory column (VRC) elicits changes in the concentrations of multiple neurochemicals, including serotonin (5-HT), substance P, glycine, and GABA, while increasing or having no effect on breathing. These findings are consistent with the concept of interdependence between neuromodulators, whereby attenuation of one modulator elicits compensatory changes in other modulators to maintain breathing. Because there is a large degree of redundancy and multiplicity of excitatory inputs to the VRC, we herein tested the hypothesis that combined unilateral blockade of muscarinic acetylcholine (mACh), neurokinin-1 (NK1, the receptor for substance P), and 5-HT2A receptors would elicit changes in multiple neurochemicals, but would not change breathing. We unilaterally reverse-dialyzed a cocktail of antagonists targeting these receptors into the VRC of intact adult goats. Breathing was continuously monitored while effluent fluid from dialysis was collected for quantification of neurochemicals. We found that neither double blockade of mACh and NK1 receptors, nor triple blockade of mACh, NK1, and 5-HT2A receptors significantly affected breathing (P ≥ 0.05) in goats that were awake or in non-rapid eye movement (NREM) sleep. However, both double and triple blockade increased the effluent concentration of substance P (P < 0.001) and decreased GABA concentrations. These findings support our hypothesis and, together with past data, suggest that both in wakefulness and NREM sleep, multiple neuromodulator systems collaborate to stabilize breathing when a deficit in one or multiple excitatory neuromodulators exists.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Clarissa
authors.initials: C
authors.lastname: Muere
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Suzanne
authors.initials: S
authors.lastname: Neumueller
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Samantha
authors.initials: S
authors.lastname: Olesiak
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin.
authors.forename: Justin
authors.initials: J
authors.lastname: Miller
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Thomas
authors.initials: T
authors.lastname: Langer
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hodges
authors.affiliation: Department of Physical Therapy, Marquette University, Milwaukee, Wisconsin; and.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin bforster@mcw.edu.
authors.forename: Hubert V
authors.initials: HV
authors.lastname: Forster
mesh_terms: D000818:Animals; D018680:Cholinergic Antagonists / Q000008:administration & dosage; D005260:Female; D006041:Goats / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*
chemical_list: D018680:Cholinergic Antagonists; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists
keywords: 5-HT2A receptor; muscarinic receptor; neurokinin-1 receptor; neuromodulation