Cotinine enhances the nicotine‐mediated decrease in respiratory burst amplitude recorded from the hypoglossal nerve in the brainstem spinal cord preparation from nicotine‐exposed neonatal rats

Abstract

Cotinine, the primary metabolite of nicotine, can be detected in the blood of infants born to mothers who used nicotine products during pregnancy and breast feeding, and is used as a marker of nicotine exposure. Previous research shows that prenatal nicotine exposure alters the regions of the brain that control breathing and results in impaired protective breathing reflexes in exposed human and animal neonates. These abnormalities are proposed as a mechanism to explain Sudden Infant Death Syndrome (SIDS), and maternal smoking is the number one risk factor for SIDS. While it has long been known that nicotine has direct effects on brain function and development, it has only recently been established that cotinine may act on the brain as well. Both nicotine and cotinine bind to nicotinic acetylcholine receptors (nAChRs) which are expressed on neurons throughout the nervous system. Preliminary data using the in vitro brainstem spinal‐cord preparation from nicotine‐exposed neonatal rats shows that activation of nAChRs produces a decrease in the amplitude of respiratory bursts recorded from hypoglossal nerve roots (−30.74±18.2 % baseline, n=4), and that this effect is enhanced by cotinine (−60.34±16.1 % baseline, n=4). This supports the hypothesis that cotinine modulates the function of nAChRs in regions of the brain that control breathing (P<0.0001).Support or Funding Information5R01HD071302‐07