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Cited by 17Nicotinic Acetylcholine Receptors StudyPrenatal Substance Exposure EffectsNeuroscience and Neuropharmacology Research

Electrophysiological changes in laterodorsal tegmental neurons associated with prenatal nicotine exposure: Implications for heightened susceptibility to addict to drugs of abuse

Christensen, M. H., Nielsen, M. L., Kohlmeier, K. A.·2015·Journal of Developmental Origins of Health and Disease
DOI 10.1017/s204017441400049x
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Abstract

Prenatal nicotine exposure (PNE) is a risk factor for developing an addiction to nicotine at a later stage in life. Understanding the neurobiological changes in reward related circuitry induced by exposure to nicotine prenatally is vital if we are to combat the heightened addiction liability in these vulnerable individuals. The laterodorsal tegmental nucleus (LDT), which is comprised of cholinergic, GABAergic and glutamatergic neurons, is importantly involved in reward mediation via demonstrated excitatory projections to dopamine-containing ventral tegmental neurons. PNE could lead to alterations in LDT neurons that would be expected to alter responses to later-life nicotine exposure. To examine this issue, we monitored nicotine-induced responses of LDT neurons in brain slices of PNE and drug naive mice using calcium imaging and whole-cell patch clamping. Nicotine was found to induce rises in calcium in a smaller proportion of LDT cells in PNE mice aged 7-15 days and smaller rises in calcium in PNE animals from postnatal ages 11-21 days when compared with age-matched control animals. While inward currents induced by nicotine were not found to be different, nicotine did induce larger amplitude excitatory postsynaptic currents in PNE animals in the oldest age group when compared with amplitudes induced in similar-aged control animals. Immunohistochemically identified cholinergic LDT cells from PNE animals exhibited slower spike rise and decay slopes, which likely contributed to the wider action potential observed. Further, PNE was associated with a more negative action potential afterhyperpolarization in cholinergic cells. Interestingly, the changes found in these parameters in animals exposed prenatally to nicotine were age related, in that they were not apparent in animals from the oldest age group examined. Taken together, our data suggest that PNE induces changes in cholinergic LDT cells that would be expected to alter cellular excitability. As the changes are age related, these PNE-associated alterations could contribute differentially across ontogeny to nicotine-mediated reward and may contribute to the particular susceptibility of in utero nicotine exposed individuals to addict to nicotine upon nicotine exposure in the juvenile period.

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  • Electrophysiological analysis of in vitro brain slices has shown that oral nicotine (300 μg/ml) exposure throughout gestation reduces nicotine-induced intracellular calcium and AMPA-mediated glutamate responses in LDTg neurons.

    “Electrophysiological analysis of in vitro brain slices has shown that oral nicotine (300 μg/ml) exposure throughout gestation reduces nicotine-induced intracellular calcium and AMPA-mediated glutamate responses in LDTg neurons [44,45].”

    From Nicotine on the developing brain. (2023) · cites this paper as [44]

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Authors
Christensen, M. H., Nielsen, M. L., & Kohlmeier, K. A.
Affiliations
University of Copenhagen (DK)
Corresponding author
Kohlmeier, K. A.
ORCID
Venue
Journal of Developmental Origins of Health and Disease
Publisher
Cambridge University Press (CUP)
Published
2014-10-23
Volume
6
Issue
3
Pages
182-200
ISSN
  • 2040-1744 (ISSN-L)
  • 2040-1752
DOI
10.1017/s204017441400049x
OpenAlex
W2110714212
Cited by
17
References
112
Citations by year
2026: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2016: 1 · 2015: 1 · 2014: 2
FWCI
0.55
Type
journal article
Language
en
Open access
closed
Licence
www.cambridge.org/core/terms (unspecified)
Locations
  • Journal of Developmental Origins of Health and Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
prenatal nicotine exposure, laterodorsal tegmental nucleus, cholinergic neurons, neuronal excitability, calcium imaging, excitatory postsynaptic currents, reward systems, ontogeny
MeSH terms
Animals, Calcium, Female, Humans, Nicotine, Pregnancy, Prenatal Exposure Delayed Effects, Tegmentum Mesencephali, Behavior, Addictive, Patch-Clamp Techniques, Excitatory Postsynaptic Potentials, Mice, Electrophysiological Phenomena

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