Nicotine administration differentially affects gene expression in the maternal and fetal circadian clock

D. A. Clegg, B. F. O'Hara, H. C. Heller, T. S. Kilduff

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Exposure to nicotine by active and passive cigarette smoke is a common public health problem. Recent studies have demonstrated that human fetuses are also exposed to significant levels of nicotine and that there is a five-fold increase in the incidence of Sudden Infant Death Syndrome among infants born to smoking mothers. We examined the effect of nicotine administration and expression of the immediate early gene c-fos in the maternal and fetal rat brain by in situ hybridization. Nicotine injection (1 mg/kg s.c.) on embryonic day 20 (E20) induced detectable c-fos mRNA in the maternal habenula and hypothalamic paraventricular nucleus whereas, in the fetal brain, c-fos was induced in both these structures and also in the suprachiasmatic nucleus (SCN). Nicotine-induced c-fos expression in the fetal SCN was confirmed by Northern analysis and found to return to near basal levels by 3 h post-injection. These responses were blocked by pre-administration of mecamylamine, indicating that the effect of nicotine is mediated through the cholinergic system. Investigation of the development of this response revealed that nicotine failed to induce c-fos expression in the SCN on E16, caused minimal expression on E18, robust expression on E20 and postnatal day 0 (P0), and no expression on P2 or thereafter. These observations suggest that an alteration in the composition of the nicotinic receptors (nAChR), or the subsequent intracellular responses leading to c-fos expression, occurs in the SCN during the perinatal period. Induction of c-fos mRNA in the SCN by light has been associated with phase-shifts of the circadian system, however, the behavioral consequences of the transient sensitivity of the fetal and neonatal SCN to nicotine administration and the consequences for maternal-fetal entrainment remain to be directly determined.

Original languageEnglish
Pages (from-to)46-54
Number of pages9
JournalDevelopmental Brain Research
Issue number1
StatePublished - Jan 14 1995


  • Biological clock
  • Circadian rhythm
  • Light
  • SCN
  • SIDS
  • c-fos

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology


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