NICOTINE ADMINISTRATION DIFFERENTIALLY AFFECTS GENE-EXPRESSION IN THEMATERNAL AND FETAL CIRCADIAN CLOCK

Exposure to nicotine by active and passive cigarette smoke is a common public health problem. Recent studies have demonstrated that human fe tuses are also exposed to significant levels of nicotine and that ther e is a five-fold increase in the incidence of Sudden Infant Death Synd rome among infants born to smoking mothers. We examined the effect of nicotine administration and expression of the immediate early gene c-f os in the maternal and fetal rat brain by in situ hybridization. Nicot ine injection (1 mg/kg s.c.) on embryonic day 20 (E20) induced detecta ble c-fos mRNA in the maternal habenula and hypothalamic paraventricul ar nucleus whereas, in the fetal brain, c-fos was induced in both thes e structures and also in the suprachiasmatic nucleus (SCN). Nicotine-i nduced c-fos expression in the fetal SCN was confirmed by Northern ana lysis and found to return to near basal levels by 3 h post-injection. These responses were blocked by pre-administration of mecamylamine, in dicating that the effect of nicotine is mediated through the cholinerg ic system. Investigation of the development of this response revealed that nicotine failed to induce c-fos expression in the SCN on E16, cau sed 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 recepto rs (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-shift s of the circadian system, however, the behavioral consequences of the transient sensitivity of the fetal and neonatal SCN to nicotine admin istration and the consequences for maternal-fetal entrainment remain t o be directly determined.