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Inhibition of medullary raphé serotonergic neurons has age-dependent effects on the CO₂ response in newborn piglets

Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756

Submitted 30 July 2003 ; accepted in final form 21 January 2004

Medullary raphé serotonergic neurons are chemosensitive in culture and are situated adjacent to blood vessels in the brain stem. Selective lesioning of serotonergic raphé neurons decreases the ventilatory response to systemic CO₂ in awake and sleeping adult rats. Abnormalities in the medullary serotonergic system, including the raphé, have been implicated in the sudden infant death syndrome (48). In this study, we ask whether serotonergic neurons in the medullary raphé and extra-raphé regions are involved in the CO₂ response in unanesthetized newborn piglets, 3-16 days old. Whole body plethysmography was used to examine the ventilatory response to 5% CO₂ before and during focal inhibition of serotonergic neurons by 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT), a 5-HT_1A receptor agonist. 8-OH-DPAT (10 or 30 mM in artificial cerebrospinal fluid) decreased the CO₂ response in wakefulness in an age-dependent manner, as revealed by a linear regression analysis that showed a significant negative correlation (P < 0.001) between the percent change in the CO₂ response and piglet age. Younger piglets showed an exaggerated CO₂ response. Control dialysis with artificial cerebrospinal fluid had no significant effect on the CO₂ response. Additionally, 8-OH-DPAT increased blood pressure and decreased heart rate independent of age (P < 0.05). Finally, sleep cycling was disrupted by 8-OH-DPAT, such that piglets were awake more and asleep less (P < 0.05). Because of the fragmentary sleep data, it was not possible to examine the CO₂ response in sleep. Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO₂ sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome.

brain stem; 8-hydroxy-2-di-n-propylaminotetralin; 5-HT_1A receptor; homeostatic physiology; sudden infant death syndrome

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