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Impact of prenatal nicotine on the structure of midbrain dopamine regions in the rat

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Abstract

In utero exposure of rats to nicotine (NIC) provides a useful animal model for studying the impact of smoking during pregnancy on human offspring. Certain sequelae of prenatal NIC exposure suggest an impact on the development of the midbrain dopamine (DA) system, which receives a robust cholinergic innervation from the mesopontine tegmentum. We therefore investigated whether prenatal NIC induced structural changes in cells and synapses within the midbrain that persisted into adulthood. Osmotic minipumps delivering either sodium bitartrate (vehicle; VEH) or NIC bitartrate at 2 mg/kg/day were implanted into nine timed-pregnant dams at E4. At birth, rat pups were culled to litters of six males each, and the litters were cross-fostered. Plasma levels of NIC and cotinine from killed pups provided evidence of NIC exposure in utero. Pups separated from dams at weaning showed a trend toward reduced locomotor activity at this time point but not when tested again in adulthood. Adult rats were killed for anatomical studies. Estimates of brain size and volume did not vary with NIC treatment. Midbrain sections stained for Nissl or by immunoperoxidase for tyrosine hydroxylase and analyzed using unbiased stereology revealed no changes in volume or cell number in the substantia nigra compacta or ventral tegmental area as a result of NIC exposure. Within the ventral tegmental area, electron microscopic physical disector analysis showed no significant differences in the number of axon terminals or the number of asymmetric (putative excitatory) or symmetric (putative inhibitory) synapses. Although too infrequent to estimate by unbiased stereology, no obvious difference in the proportion of cholinergic axons was noted in NIC- versus VEH-treated animals. These data suggest that activation of nicotinic receptors during prenatal development induces no significant modifications in the structure of cells in the ventral midbrain when assessed in adulthood.

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Acknowledgments

Grant support: USPHS grant DA021276.

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Authors and Affiliations

  1. Department of Neuroscience, Langley Hall, Room 210, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Natalia Omelchenko, Priya Roy, Judith Joyce Balcita-Pedicino & Susan R. Sesack

  2. Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Samuel Poloyac

  3. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Susan R. Sesack

  4. Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV, 26074, USA

    Natalia Omelchenko

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  1. Natalia Omelchenko
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  2. Priya Roy
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  3. Judith Joyce Balcita-Pedicino
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  4. Samuel Poloyac
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  5. Susan R. Sesack
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Correspondence to Susan R. Sesack.

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Omelchenko, N., Roy, P., Balcita-Pedicino, J.J. et al. Impact of prenatal nicotine on the structure of midbrain dopamine regions in the rat. Brain Struct Funct 221, 1939–1953 (2016). https://doi.org/10.1007/s00429-015-1014-y

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  • DOI: https://doi.org/10.1007/s00429-015-1014-y

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