The role of 5-HT in inducing apnoeas (a major element in sudden infant death syndrome) is controversial because while 5-HT is a respiratory depressant in vivo, it evokes respiratory analeptic effects when applied to the isolated brainstem of the newborn rat. In decerebrate newborn rats, the electrical activity of the diaphragm and that of a hypoglossally innervated tongue muscle, as well as the cardiac frequency (Fc), were recorded before and after the application of 5-HT and related agents to the floor of the IVth ventricle. To assess the spontaneous variability in inspiratory frequency (Fi) and Fc, a sham group was studied. A decrease in Fi was observed in response to 5-HT. This respiratory depressant effect was associated with an activation of the tongue muscle, but there was no change in Fc. Application of agonists elicited a small increase in Fi linked to activation of 5-HT1A receptors, and decreases in both Fi and the activity of the tongue muscle resulting predominantly from activation of 5-HT2 receptors. The decrease in Fi was much smaller in newborn rats than that reported in newborn kittens. Indeed, in newborn rats, we did not observe long-lasting apnoeas. Our results differ from those obtained from the newborn rat in vitro, inasmuch as in vivo 5-HT essentially depressed the respiratory rhythm generator. The role of the afferent system appears to be crucial in modulating the action of 5-HT.
1. In decerebrate kittens (it = 29), electrical activity" was studied in the 3rd intercartilaginous (inspiratory), the 9th internal intercostal (expiratory) and the hypoglossally innervated muscles (geniohyoid m. and sternohyoid m.) evoked by the application of 5-HT (a = 16) or related agents (5-HTlA agonist, 8-OH-DPAT (a7 = 6) and 5-HT2 agonist, DOI (n = 4)) to the floor of the IVth ventricle. 2. The application of a control solution (n = 2) produced no significant changes either in minute inspiratory frequency (F1) or in the electrical activity of the muscles studied. Except for these controls, only one trial with one dose of one drug was performed in a given kitten. 3. A dose-related decrease in Fi was observed in response to 5-HT. Low doses (50-500 nmol,
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