Pre‐ and early postnatal nicotine exposure exacerbates autoresuscitation failure in serotonin‐deficient rat neonates

Key points Sudden infant death syndrome (SIDS) is one of the leading causes of death during the first year of life and abnormalities linked to serotonin (5‐HT) have been identified in many SIDS cases. Cigarette smoking and associated exogenous stressors, e.g. developmental nicotine exposure, may compound these serotonergic defects and any associated defects in cardiorespiratory function. Using neonatal rodent pups subjected to medullary 5‐HT deficiency and perinatal nicotine exposure, we examined the impact of this interplay of factors on the neonates’ ability to autoresuscitate at specific ages. In perinatal nicotine‐exposed 5‐HT deficient pups, impaired autoresuscitation along with significantly delayed post‐anoxic recovery of normal breathing and heart rate was observed at postnatal day 10 (P10). We found that the interaction between 5‐HT deficiency and perinatal nicotine exposure can significantly increase pups’ vulnerability to environmental stressors and exacerbate defects in cardiorespiratory protective reflexes to repetitive anoxia during the development period.Abstract Cigarette smoking during pregnancy increases the risk of sudden infant death syndrome (SIDS), and nicotine replacements, a key ingredient of cigarettes, have been recently prescribed to women who wish to quit smoking during their pregnancy. Serotonin (5‐HT) abnormalities have been consistently identified in many SIDS cases. Here we investigated the effects of perinatal nicotine exposure in mild 5‐HT deficiency rat neonates on autoresuscitation, a protective cardiorespiratory reflex. The mild 5‐HT deficiency was induced by a maternal tryptophan‐deficient diet, and nicotine was delivered from embryonic day (E) 4 to postnatal day (P) 10 at 6 mg kg −1  day −1 through an osmotic pump. In P10 rats, nicotine exposure exacerbates autoresuscitation failure (mortality) in mildly 5‐HT‐deficient rats to a greater extent than in controls ( P  = 0.029). The recovery of eupnoea and heart rate to baseline values following repetitive anoxic events (which elicit an apnoea accompanied by a bradycardia) is significantly delayed in 5‐HT‐deficient rats treated with nicotine, making them more susceptible to failure of autoresuscitation (eupnoea recovery: P  = 0.0053; heart rate recovery: P  = < 0.0001). Neither 5‐HT deficiency nor nicotine exposure alone appears to affect the ability to autoresuscitate significantly when compared among the four treatments. The increased vulnerability to environmental stressors, e.g. severe hypoxia, asphyxia, or anoxia, in these nicotine‐exposed 5‐HT‐deficient neonates during postnatal developmental period is evident.