Prenatal nicotine exposure alters glycinergic and GABAergic control of respiratory frequency in the neonatal rat brainstem-spinal cord preparation

Respir Physiol Neurobiol. 2007 Aug 1;157(2-3):226-34. doi: 10.1016/j.resp.2007.01.005. Epub 2007 Jan 12.


Bath application of GABA-A receptor agonists in neonatal rat brainstem-spinal cord preparations (BSSC) reduces respiratory frequency, an effect that is enhanced by prenatal nicotine exposure. Here we test the hypothesis that these effects can be reproduced by microinjection of GABAergic and glycinergic agonists into the pre-Botzinger complex region (PBC). We recorded the activity of phrenic motor axons from the fourth cervical ventral root in 1-3 days old BSSC that were exposed to either nicotine (6 mg/(kg day)) or saline prenatally. Microinjection of glycine or muscimol into the PBC caused abrupt, reversible apnea in all experiments. Apnea duration with glycine averaged 50.3+/-5 s in saline-exposed (N=12), and 95.7+/-9.9 s in nicotine-exposed (N=12) neonates (P<0.001). Apnea duration with muscimol averaged 51+/-5.1 s in saline-exposed (N=10), and 86+/-10.6 s in nicotine-exposed (N=12) neonates (P<0.05). These data show that prenatal nicotine exposure alters development of central ventilatory control, and that neurons in the PBC region are involved.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Brain Stem / drug effects*
  • Brain Stem / physiology
  • Drug Interactions
  • Female
  • Glycine / metabolism*
  • Glycine / pharmacology
  • Glycine Agents / pharmacology
  • In Vitro Techniques
  • Microinjections
  • Models, Biological
  • Nicotine*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Respiration / drug effects*
  • Spinal Cord / drug effects*
  • Spinal Cord / physiology
  • Strychnine / pharmacology
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / pharmacology


  • Glycine Agents
  • gamma-Aminobutyric Acid
  • Nicotine
  • Strychnine
  • Glycine