BIOCHEMICAL-CHANGES, EARLY BRAIN GROWTH SUPPRESSION AND IMPAIRED DETOUR LEARNING IN NICOTINE-TREATED CHICKS

Fetal growth suppression associated with chronic maternal intake of ci garette smoke is frequently observed in humans and studies using anima l models suggest that in utero nicotine exposure is an important compo nent of this growth suppression. The developing fetal central nervous system (CNS) is sensitive to the growth inhibitory effect of nicotine and morphological as well as. functional CNS deficits may result from fetal nicotine exposure. The studies presented here show that nicotine exposure during early embryonic development ultimately inhibits the a bility of 7-11 day old chicks to learn a detour task. The brain growth suppression caused by nicotine is paralleled by a failure of the earl y embryo brain to express the normal developmental increase in ornithi ne decarboxylase (ODC) activity. This biochemical change may be german e to the mechanism of nicotine-induced growth inhibition and/or nicoti ne-induced behavioral changes because the appropriate expression of OD C activity is essential to normal growth and differentiation in the fe tal CNS. In the chick embryo, nicotine exposure alters several importa nt signaling pathways that regulate ODC expression. For example, nicot ine exposure lowers embryonic brain glucose levels and causes signific ant decreases in whole brain cyclic adenosine 3',5'-monophosphate (cyc lic AMP) levels and in cyclic AMP binding proteins (protein kinase-A r egulatory activity). Also, in cultured chick cells, nicotine inhibits the ability of a potent mitogen (insulin) to induce ODC activity, but, paradoxically, in ovo nicotine exposure increased insulin binding and stimulated insulin receptor autophosphorylation in brain membranes.