Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of hypoglossal inspiratory output in mice

J Physiol. 2002 Feb 1;538(Pt 3):957-73. doi: 10.1113/jphysiol.2001.012705.


We examined the effects of in utero nicotine exposure on postnatal development of breathing pattern and ventilatory responses to hypoxia (7.4 % O2) using whole-body plethysmography in mice at postnatal day 0 (P0), P3, P9, P19 and P42. Nicotine delayed early postnatal changes in breathing pattern. During normoxia, control and nicotine-exposed P0 mice exhibited a high frequency of apnoea (f(A)) which declined by P3 in control animals (from 6.7 +/- 0.7 to 2.2 +/- 0.7 min(-1)) but persisted in P3 nicotine-exposed animals (5.4 +/- 1.3 min(-1)). Hypoxia induced a rapid and sustained reduction in f(A) except in P0 nicotine-exposed animals where it fell initially and then increased throughout the hypoxic period. During recovery, f(A) increased above control levels in both groups at P0. By P3 this increase was reduced in control but persisted in nicotine-exposed animals. To examine the origin of differences in respiratory behaviour, we compared the activity of hypoglossal (XII) nerves and motoneurons in medullary slice preparations. The frequency and variability of the respiratory rhythm and the envelope of inspiratory activity in XII nerves and motoneurons were indistinguishable between control and nicotine-exposed animals. Activation of postsynaptic nicotine receptors caused an inward current in XII motoneurons that potentiated XII nerve burst amplitude by 25 +/- 5 % in control but only 14 +/- 3 % in nicotine-exposed animals. Increased apnoea following nicotine exposure does not appear to reflect changes in basal activity of rhythm or pattern-generating networks, but may result, in part, from reduced nicotinic modulation of XII motoneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / growth & development
  • Apnea / epidemiology
  • Apnea / physiopathology*
  • Brain / drug effects
  • Brain / physiopathology
  • Embryonic and Fetal Development / drug effects
  • Female
  • Hypoglossal Nerve / physiopathology*
  • Hypoxia / chemically induced
  • Hypoxia / physiopathology
  • In Vitro Techniques
  • Incidence
  • Inhalation*
  • Mice / embryology
  • Motor Neurons / drug effects
  • Motor Neurons / physiology
  • Neurons / physiology
  • Nicotine / administration & dosage
  • Nicotine / blood
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Receptors, Nicotinic / physiology*
  • Respiration / drug effects
  • Respiratory Physiological Phenomena
  • Time Factors


  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Nicotine