Serotoninergic and non‐serotoninergic responses of phrenic motoneurones to raphe stimulation in the cat.

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Abstract
Experiments were conducted on anesthetized, paralyzed and artificially ventilated cats in order to determine if the altered discharge pattern of phrenic motoneurons recorded during stimulation of medullary raphe nuclei (raphe magnus (r. magnus), raphe obscurus (r. obscurus), raphe pallidus (r. pallidus)) are related to release of serotonin (5-hydroxytryptamine, 5-HT) at synapses on respiratory neurons. Effects of 5-HT released by the neurotoxin p-chloroamphetamine (PCA) on spontaneous activity of phrenic motoneurons were also examined. In addition, responses of phrenic motoneurons to 5-HT applied by micro-electrophoresis were recorded. Stimulation (100 Hz) of r. magnus or r. obscurus depressed the spontaneous inspiratory discharges of phrenic motoneurons. Administration of the 5-HT receptor antagonists cinanserin, methysergide or methergoline reduced, but did not abolish, the inhibition. Inhibition of the neuronal reuptake of 5-HT with fluoxetine enhanced the inhibition and reduced the peak inspiratory action potential frequency of spontaneous discharges. Stimulation (100 Hz) of r. pallidus produced increased firing of phrenic motoneurons. Firing of phrenic motoneurons was evoked even during the normally quiescent expiratory phase of spontaneous respiratory activity. Antagonists at 5-HT receptors reduced the degree of tonic firing, resulting in partial restoration of expiratory pauses during r. pallidus stimulation. Inhibition of 5-HT reuptake, on the other hand, resulted in increased tonic firing. Release of 5-HT by PCA produced a rapid and severe reduction of phrenic nerve activity. Activity was restored by 5-HT receptor antagonists. In reserpine-treated cats, effects of stimulating medullary raphe nuclei were still pronounced, however 5-HT receptor antagonists had no effect on the responses. These results, along with the observation that 5-HT receptor antagonists are only partially effective in non-reserpinized cats, indicate that non-serotoninergic influences contribute as well to the responses evoked by raphe stimulation. Micro-electrophoretic application of 5-HT by large ejecting currents (100-200 nA) had weak stimulatory effects on twenty of forty-five phrenic motoneurons, which exhibited small increases in peak inspiratory discharge frequency during 5-HT application. Ejecting currents less than 100 nA were without effect. It is concluded that 5-HT analogues and agents which release endogenous 5-HT after parenteral administration do not act directly at synapses on the soma membranes of phrenic motoneurons. .gamma.-Aminobutyric acid (GABA) and glycine applied by micro-electrophoresis produced rapid and marked depressant actions on phrenic motoneurons. However, intravenous administration of bicuculline (50-500 .mu.g/kg), a post-synaptic GABA receptor antagonist, or strychnine (80-200 .mu.g/kg), an antagonist at glycine receptors, did not antagonize the responses to medullary raphe stimulation. Therefore, the non-serotoninergic inhibitory effects of raphe stimulation do not appear to involve GABA- or glycine-mediated post-synaptic actions.