The resources on this particular topic were minute. In fact, only two articles were obtained Therefore due to the lack of compiling information, all of the following text should be attributed to the sources listed

The maternal utilization of tobacco substances during pregnancy gives rise to growth retardation and an array of neurobehavior defects in the offspring. Although concurrent exposure of the fetus to hypoxia and ischemia are major contributors to the developmental effects of smoking in man, or of injected nicotine in animals, recent studies using slow infusions of nicotine strongly suggest that nicotine affects fetal and neonatal development. Due to the action of nicotine via neurotransmitter receptors in the nervous system) the sensitivity of the developing brain is displayed in the disruption of cellular development and blunting of neural activity in central and peripheral catecholaminergic systems (Navarro et al, p894).

Many of the developmental abnormalities seen with prenatal nicotine exposure resemble those obtained through enhancement of cholinergic neuronal activity through dietary manipulations. Endogenous cholinergic input has been shown to control cellular development in cerebral cortex, the same region found to be highly sensitive to perturbations caused by nicotine or by high dietary choline. Thus, the effects of nicotine may represent the simulation of a natural developmental signal, but at an inappropriate time. A current study examines the potential interaction of prenatal nicotine exposure with the development of cholinergic neurotransmitter systems in different brain regions (Navarro et al’ p894).

The experimentation of the pregnant Sprague-Dawley rats entailed a nicotine infusion pump being placed on the control and experimental pregnant rats. Initially the nicotine infusion inhibited maternal weight gain for the first few days of implantation. Normal weight gains ensued thereafter. The nicotine had no significant effect on the proportion of pups delivered (82% in controls’ 83% in the nicotine group). At 16 days of gestation, little or no alterations of body or brain weight can be attributed to the nicotine infusion. Postnatally, there were small (5-10%) but statistically significant lags in body and brain region weights in the nicotine group, all the weight differences were resolved by the 2nd postnatal week. The ChAT activity showed distinct regional differences in development. In the cerebral cortex, the rise in activity occurred most rapidly during the 2nd to 3rd postnatal weeks; levels achieved half of the adult value by the middle to end of the 3rd week and reached adult levels at about 6 weeks postpartum. Midbrain and brainstem displayed a slightly earlier developmental profile, reaching half of adult values by the end of the 2nd week or middle of the 3rd week. The pattern in the cerebellum was different from the others, characterized by virtually no change in enzyme activity per gram of tissue. Therefore it simply paralleled the increases in development of tissue weight (Navarro et al, p895).

Exposure of developing fetuses to nicotine had an initial promotional effect on ChAT activity. As early as gestational day 18, enzyme activity in whole brain was significantly elevated; a small portion of the difference reflected a slight (not significant) lowering of brain weight in the nicotine group, and thus the assessment of activity per brain indicated only marginal significance. Significant increases in ChAT remained detectable into the immediate postnatal period; at 2 days of age, cerebral cortical activity was 0.41 0.01 mol/g/hr in controls and 0.49 0.02 in the nicotine exposed animals. Subsequent examination of the development of this enzyme in the three brain regions indicated that stimulation did not persist. Indeed, enzyme activity tended to be significantly lower in the nicotine group across all brain regions, most notably in the cerebral cortex and cerebellum during the 2nd postnatal week and after 50 days of age {Navarro et. al. , p896}.

The results obtained suggest that a surge in cholinergic activity occurs during early development of the cerebral cortex and that prenatal nicotine exposure probably disrupts cortical development by stimulating this signal prematurely. Despite the scarcity of cholinergic projections in the immediate postnatal period, the relative activity of these terminals appears to be high as measured with the uptake/ChAT ratio. The activity reached a peak just at the beginning of the major phase of synaptogenesis, coinciding with the period in which neurogenesis is supplanted by differentiation and specialization, as indicated by markers of cellular development such as ornithine decarboxylase activity and nucleic acid synthesis. This temporal relationship is obviously in keeping with a role of the cholinergic surge in cortical development, and a definitive proof of the importance of the presence of cholinergic projections during this phase has been provided recently by studies using ablation of basal forebrain cholinergic neurons (Navarro et al, p896).

If transient activation of cholinergic transmission is a regulatory event in cortical development, then it is likely that many of the adverse neural effects of prenatal nicotine exposure represent a premature elicitation of the rnaturational events ordinarily triggered by the postnatal peak of cholinergic activity. In part, this probably represents direct actions of nicotine on nicotinic receptors that are present and functionally active before birth; in addition, there appears to be a prenatal/early postnatal promotional effect on cholinergic development caused by prenatal nicotine or other cholinomimetic treatments. Prenatal nicotine exposure has a selective effect on the central nervous system development characterized by disruption of cellular maturation and long-term reductions in synaptic activity of catecholamine systems, especially in cerebral cortex; effects on the nervous system are evident even at nicotine dose levels which do not affect growth (Navarro et. al., p897).

The patterns of development of cholinergic activity may also be important in determining the regional selectivity of the effect of prenatal nicotine administration The midbrain + brainstem showed earlier neuronal development when compared to the cerebral cortex (Navarro et. al., p899).

In conclusion, the transient increases in cholinergic neuronal activity occur in developing cerebral cortex during early postnatal life. Prenatal exposure to nicotine disrupts the pattern of cholinergic development prominently in this brain region, probably contributing to the adverse effects of the drug on neurogenesis and synaptic function. The prenatal presence of nicotinic receptors may thus enable nicotine to affect development by evoking an endogenous maturational signal prematurely (Navarro et. al., p899).

Because the neurotransmitters control patterns of cell maturation in the nervous system, specifically controlling the switch over from cell replication to differentiation, the nervous system is more vulnerable than the rest of the fetus. This is an exception from the general "brain Sparing" course of action, wherein damage to a developing fetus by malnutrition, drugs and toxic chemicals has less of an growth impairment on the nervous system than the rest of the fetus (Navarro et. al., p191)

RESOURCES:

Navarro, H.A., Seidler, F.J., Schwartz, R-D., Maker, E.E., Dobbins, S-S, and Slotkin, T.A. Prenatal Exposure to Nicotine Impairs Nervous System Development at a Dose Which Does Not Affect Viability or Growth. Brain Research Bulletin, Vol. 23, pp. 137-192, 1989.

Navarro, H-A., Seidler, F.J., Eylersk, J-P., Baker, F.E., Dobbins, S.S., Lappi, S.E., and Slotkin, T.A. Effects of Prenatal Nicotine Exposure on Development of Central and Peripheral Cholinergic Neurotransmitter Systems. Evidence for Cholinergic Trophic Influences in Developing Brain. The Journal of Pharmacology and Experimental Therapeutics, Vol. 251. No.3, pp. 894-399, 1989.