The dynamic effects of nicotine on the developing brain

Dwyer, Jennifer B.; McQuown, Susan C.; Leslie, Frances M.

doi:10.1016/j.pharmthera.2009.02.003

Cited by 559Nicotinic Acetylcholine Receptors StudyPrenatal Substance Exposure EffectsSmoking Behavior and Cessation

The dynamic effects of nicotine on the developing brain

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Dwyer, Jennifer B., McQuown, Susan C., Leslie, Frances M.·2009·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2009.02.003PMC PMC2746456

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Abstract

Nicotinic acetylcholine receptors (nAChRs) regulate critical aspects of brain maturation during the prenatal, early postnatal, and adolescent periods. During these developmental windows, nAChRs are often transiently upregulated or change subunit composition in those neural structures that are undergoing major phases of differentiation and synaptogenesis, and are sensitive to environmental stimuli. Nicotine exposure, most often via tobacco smoke, but increasingly via nicotine replacement therapy, has been shown to have unique effects on the developing human brain. Consistent with a dynamic developmental role for acetylcholine, exogenous nicotine produces effects that are unique to the period of exposure and that impact the developing structures regulated by acetylcholine at that time. Here we present a review of the evidence, available from both the clinical literature and preclinical animal models, which suggests that the diverse effects of nicotine exposure are best evaluated in the context of regional and temporal expression patterns of nAChRs during sensitive maturational periods, and disruption of the normal developmental influences of acetylcholine. We present evidence that nicotine interferes with catecholamine and brainstem autonomic nuclei development during the prenatal period of the rodent (equivalent to first and second trimester of the human), alters the neocortex, hippocampus, and cerebellum during the early postnatal period (third trimester of the human), and influences limbic system and late monoamine maturation during adolescence.

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Exposure to nicotine in adolescence is associated with brain-wide changes to the expression of discrete nAChR subunits, with some transient changes appearing during treatment or withdrawal, but with some persistent changes enduring until adulthood.
“Exposure to nicotine in adolescence is associated with brain-wide changes to the expression of discrete nAChR subunits, with some transient changes appearing during treatment or withdrawal, but with some persistent changes enduring until adulthood.”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [53]
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nAChRs appear early in development and are functionally active in the fetal brain to mediate critical aspects of brain maturation.
“These receptors appear early in development and are functionally active in the fetal brain to mediate many critical aspects of brain maturation [1–4].”
From Nicotine on the developing brain. (2023) · cites this paper as [4]
nAChRs are expressed early in brain development and play critical maturational roles at many stages, including adolescence.
“nAChRs are expressed early in brain development and play critical maturational roles at many developmental stages, including adolescence (reviewed by Dwyer et al., 2009).”
From Unique, long-term effects of nicotine on adolescent brain. (2020) · cites this paper as Dwyer et al., 2009
Nicotine exposure during critical developmental periods disrupts neural development and often has long-lasting effects on associated behaviors.
“Nicotine exposure during critical developmental periods disrupts neural development, and often has long-lasting effects on associated behaviors [3–7].”
From Nicotine on the developing brain. (2023) · cites this paper as [4]
Nicotine exposure during this highly plastic state induces long term changes in critical circuitry, maturation of monoamine systems, and behavior, including reward related behaviors.
“Nicotine exposure during this highly plastic state induces long term changes in critical circuitry, maturation of monoamine systems, and behavior, including reward related behaviors (see Fig. 3) [4,6,7].”
From Nicotine on the developing brain. (2023) · cites this paper as [4]

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Authors: Dwyer, J. B., McQuown, S. C., & Leslie, F. M.
Affiliations: University of California, Irvine (US)
Corresponding author: Dwyer, Jennifer B.
ORCID: Leslie, Frances M.
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2009-05
Volume: 122
Issue: 2
Pages: 125-139
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2009.02.003
PMC: PMC2746456
OpenAlex: W2072987235
Cited by: 559
References: 279
Citations by year: 2026: 12 · 2025: 20 · 2024: 26 · 2023: 29 · 2022: 34 · 2021: 34 · 2020: 32 · 2019: 37 · 2018: 36 · 2017: 51 · 2016: 53 · 2015: 53 · 2014: 37 · 2013: 34 · 2012: 26
FWCI: 1.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (DA-10612, DA 19138, R01DA019138, R01DA010612)
National Institute of General Medical Sciences (GM08620, T32GM008620)
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
Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords: nicotine, nicotinic acetylcholine receptors, brain development, prenatal nicotine exposure, postnatal development, adolescence, acetylcholine, neocortex, hippocampus, cerebellum, limbic system, nicotine replacement therapy, tobacco smoke, synaptogenesis
MeSH terms: Adolescent, Animals, Brain, Humans, Infant, Infant, Newborn, Nicotine, Receptors, Nicotinic, Fetal Development, Rats

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The dynamic effects of nicotine on the developing brain

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