Muscimol dialysis in the retrotrapezoid nucleus region inhibits breathing in the awake rat.
Under anesthesia, inactivation of the retrotrapezoid nucleus (RTN) region markedly inhibits breathing and chemoreception. In conscious rats, we dialyzed muscimol for 30 min to inhibit neurons of the RTN region reversibly. Dialysis of artificial cerebrospinal fluid had no effect. Muscimol (1 or 10 mM) significantly decreased tidal volume (VT) (by 16-17%) within 15 min. VT remained decreased for 50 min or more, with recovery by 90 min. Ventilation (VE) decreased significantly (by 15-20%) within 15 min and then returned to baseline within 40 min as a result of an increase in frequency. This, we suggest, is a compensatory physiological response to the reduced VT. Oxygen consumption was unchanged. In response to 7% CO(2) in the 1 mM group, absolute VE and change in VE were significantly reduced (by 19-22%). In the 10 mM group, the response to dialysis included a time-related increase in frequency and decrease in body temperature, which may reflect greater spread of muscimol. In the awake rat, the RTN region provides a portion of the tonic drive to breathe, as well as a portion of the response to hypercapnia.
Nattie
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Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA. eugene.nattie@dartmouth.edu
Li
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D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D002555:Cerebrospinal Fluid; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology*; D006935:Hypercapnia / Q000503:physiopathology; D007040:Hypoventilation / Q000139:chemically induced / Q000503:physiopathology; D008526:Medulla Oblongata / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D017551:Microdialysis; D009118:Muscimol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D012125:Respiratory Center / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000502:physiology
D018755:GABA Agonists; D011963:Receptors, GABA-A; D002245:Carbon Dioxide; D009118:Muscimol