title: Serotonin and noradrenaline modulate respiratory pattern disturbances evoked by glutamate injection into the pedunculopontine tegmentum of anesthetized rats.
abstract: OBJECTIVE
  We hypothesized that 2 important neurotransmitters related to behavioral state control, serotonin and noradrenaline, could also be modulators of pedunculopontine tegmental nucleus (PPT)-induced respiratory dysrhythmia.
  
  
  METHODS
  We examined the impact of serotonin and noradrenaline at respiratory control sites in the PPT functionally identified by immediate apnea of 2.5- to 10-second duration, followed by increased variability of breath time (CVT(T)) (P < .04) after locally injecting glutamate in anesthetized rats.
  
  
  METHODS
  Basic sleep and respiratory neurobiology laboratory.
  
  
  METHODS
  Sixteen adult, male Sprague-Dawley rats.
  
  
  RESULTS
  Glutamate-induced respiratory responses, including increases of total apnea duration and CVT(T), were not different between groups of rats in which we further tested monoaminergic modulatory effects (for CVT(T) P = .98, and for total apnea duration, P = .80). Serotonin or noradrenaline injected at the same sites as glutamate had equal impact on CVT(T) (P = .34) and on mean total apnea duration (P = .80), but pretreatment of PPT sites with serotonin blocked (remained equal to preinjection; P = .11), whereas pretreatment with noradrenaline potentiated (P = .04) the increment of respiratory-timing variability induced by glutamate. The serotonergic-blocking effect on glutamate-induced respiratory dysrhythmia was specific to the PPT: the respiratory responses induced by glutamate injection outside the PPT were not modulated by serotonin (for CVT(T), P = .46, and for mean apnea duration, P = .99).
  
  
  CONCLUSIONS
  The opposed impact of serotonin and noradrenaline on PPT-induced respiratory dysrhythmia, in contrast to their convergent regulatory role in behavioral state control, suggests a functionally distinct role for the PPT in respiratory-pattern control independent of rapid eye movement sleep control.
authors.affiliation: Section of Respiratory and Critical Care Medicine, Department of Medicine (MC 719), 840 South Wood Street, Chicago, Illinois 60612-7323, USA. jasnasap@uic.edu
authors.forename: Jasna
authors.initials: J
authors.lastname: Saponjic
authors.forename: Jovana
authors.initials: J
authors.lastname: Cvorovic
authors.forename: Miodrag
authors.initials: M
authors.lastname: Radulovacki
authors.forename: David W
authors.initials: DW
authors.lastname: Carley
mesh_terms: D000758:Anesthesia; D000818:Animals; D018698:Glutamic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D007267:Injections; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012120:Respiration Disorders / Q000139:chemically induced*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D012701:Serotonin; D018698:Glutamic Acid; D009638:Norepinephrine