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J Appl Physiol (January 29, 2004). doi:10.1152/japplphysiol.00805.2003
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Submitted on July 30, 2003
Accepted on January 21, 2004

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

Michelle L Messier1*, Aihua Li1, and Eugene E Nattie1

1 Department of Physiology, Dartmouth Medical School, Lebanon, NH, USA

* To whom correspondence should be addressed. E-mail: Michelle.L.Messier.Adv03{at}Alum.Dartmouth.ORG.

Medullary raphe serotonergic neurons are chemosensitive in culture (65) and are situated adjacent to blood vessels in the brainstem (8). Selective lesioning of serotonergic raphe neurons decreases the ventilatory response to systemic CO2 in awake and sleeping adult rats (47). Abnormalities in the medullary serotonergic system, including the raphe, have been implicated in the Sudden Infant Death Syndrome (SIDS) (48). In this study, we ask if serotonergic neurons in the medullary raphe and extra-raphe 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-HT1A receptor agonist. 8-OH-DPAT (10 or 30mM 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 aCSF 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 raphe and extra-raphe neurons decreases ventilatory CO2 sensitivity, and alters cardiovascular variables and sleep cycling, which may contribute to SIDS.




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