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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Serotonin and noradrenaline modulate respiratory pattern disturbances evoked by glutamate injection into the pedunculopontine tegmentum of anesthetized rats.

STUDY OBJECTIVES: 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. DESIGN: 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. SETTING: Basic sleep and respiratory neurobiology laboratory. PARTICIPANTS: Sixteen adult, male Sprague-Dawley rats. MEASUREMENTS AND 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.[1]


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