Altered respiratory activity and respiratory regulations in adult monoamine oxidase A-deficient mice

The abnormal metabolism of serotonin during the perinatal period alters res piratory network maturation at birth as revealed by comparing the monoamine oxidase A-deficient transgenic (Tg8) with the control (C3H) mice (Bou-Flor es et al., 2000). To know whether these alterations occur only transiently or induce persistent respiratory dysfunction during adulthood, we studied t he respiratory activity and regulations in adult C3H and Tg8 mice. First, p lethysmographic and pneumotachographic analyses of breathing patterns revea led weaker tidal volumes and shorter inspiratory durations in Tg8 than in C 3H mice. Second, electrophysiological studies showed that the firing activi ty of inspiratory medullary neurons and phrenic motoneurons is higher in Tg 8 mice and that of the intercostal motoneurons in C3H mice. Third, histolog ical studies indicated abnormally large cell bodies of Tg8 intercostal but not phrenic motoneurons. Finally, respiratory responses to hypoxia and lung inflation are weaker in Tg8 than in C3H mice. DL-p-chlorophenyl-alanine tr eatments applied to Tg8 mice depress the high serotonin level present durin g adulthood; the treated mice recover normal respiratory responses to both hypoxia and lung inflation, but their breathing parameters are not signific antly affected. Therefore in Tg8 mice the high serotonin level occurring du ring the perinatal period alters respiratory network maturation and produce s a permanent respiratory dysfunction, whereas the high serotonin level pre sent in adults alters the respiratory regulatory processes. In conclusion, the metabolism of serotonin plays a crucial role in the maturation of the r espiratory network and in both the respiratory activity and the respiratory regulations.