Changes in serotoninergic receptors 1A and 2A in the piglet brainstem after intermittent hypercapnic hypoxia (IHH) and nicotine

We studied the effects of intermittent hypercapnic hypoxia (IHH) and/or nicotine on the immunoreactivity of serotoninergic (5-HT) receptors 1A and 2A in the piglet brainstem. These exposures were developed to mimic two common risk factors for Sudden Infant Death Syndrome (SIDS); prone sleeping (IHH) and cigarette smoke exposure (nicotine). Immunoreactivity for 5-HT1AR and 5-HT2AR were studied in four nuclei of the caudal medulla. Three exposure groups were compared to controls (n = 14): IHH (n = 10), nicotine (n = 14), and nicotine + IHH (n = 14). In control piglets, the immunoreactivity of 5-HT1AR was highest in the hypoglossal nucleus (XII), followed by inferior olivary nucleus (ION), nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus (DMNV), whereas for 5-HT2AR, the immunoreactivity was highest in DMNV/NTS and then ION. Compared to controls, IHH reduced 5-HT1AR immunoreactivity in all studied nuclei (p < 0.05) but had no effect on 5-HT2AR immunoreactivity. Nicotine reduced 5-HT1AR immunoreactivity in the DMNV, ION and NTS (p < 0.001), and reduced 5-HT2AR immunoreactivity in DMNV/NTS (p < 0.05). Nicotine + IHH reduced 5-HT1AR in DMNV, ION and NTS (p < 0.001) but had no effect on 5-HT2AR immunoreactivity. Effects of nicotine on the DMNV were more significant in males compared to the females. These results show for the first time that IHH and/or nicotine can reduce 5-HT receptor immunoreactivity within functionally important nuclei of the piglet medulla. The findings support our hypothesis that 5-HT receptor abnormalities may be caused by postnatal exposures to clinically-relevant stimuli such as cigarette smoke exposure and/or prone sleeping.