Nicotine exposure during adolescence alters the rules for prefrontal cortical synaptic plasticity during adulthood
Open accessAbstract
The majority of adolescents report to have smoked a cigarette at least once. Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age may compromise the normal course of prefrontal development and lead to cognitive impairments in later life. In addition, adolescent smokers suffer from attention deficits, which progress with the years of smoking. Recent studies in rodents reveal the molecular changes induced by adolescent nicotine exposure that alter the functioning of synapses in the PFC and underlie the lasting effects on cognitive function. In particular, the expression and function of metabotropic glutamate receptors (mGluRs) are changed and this has an impact on short- and long-term plasticity of glutamatergic synapses in the PFC and ultimately on the attention performance. Here, we review and discuss these recent findings.
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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 [114]
The ‘Upregulation of nAChR and synaptic mGluR expression’ section reports short-term increases in α4- and β2-containing nAChRs in adolescent rodent mPFC and mentions acute and longer-lasting changes in receptor binding in regions such as cortex and striatum. It does not establish brain-wide, subunit-specific expression changes persisting into adulthood. The ‘Lasting synaptic adaptations in the PFC’ section instead says PFC nAChR levels returned to baseline five weeks after exposure; the persistent change described there is in mGluR2. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe peripubertal period marks a time of unique vulnerability to the long-term effects of drug exposure in a variety of animal models.
“While pubertal hormones affect propensity for drug self-administration, the peripubertal period also marks a time of unique vulnerability to the long-term effects of drug exposure in a variety of animal models.”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Goriounova and Mansvelder, 2012
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Bergstrom, H. C., McDonald, C. G., French, H. T., & Smith, R. F. (2008) · Synapse · doi:10.1002/syn.20467 · Cited by 60 · see citing works
Enhanced nicotine reward in adulthood after exposure to nicotine during early adolescence in mice
Kota, D., Robinson, S. E., & Imad Damaj, M. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.06.099 · Cited by 59 · cited 3× · see citing works
“, 2008) and function (Kota et al., 2009) in brain regions such as cortex and striatum.”
BackgroundOrr, D. P., & Ingersoll, G. M. (1995) · Pediatrics · doi:10.1542/peds.95.4.528 · Cited by 55 · cited 1× · see citing works
“Thereby, brain development may be responsible for characteristic adolescent traits—uncontrollable mood swings, impulsivity, risk-taking, and peer-directed social interactions (Orr and Ingersoll, 1995; Spear, 2000; Galvan et al., 2007).”
BackgroundNicotinic receptors and hippocampal synaptic plasticity…it’s all in the timing
McGehee, D. S. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)02127-5 · Cited by 53 · see citing works
Goriounova, N. A., & Mansvelder, H. D. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5502-11.2012 · Cited by 51 · see citing works
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Counotte, D. S., Goriounova, N. A., Moretti, M., Smoluch, M. T., Irth, H., Clementi, F., Schoffelmeer, A. N. M., Mansvelder, H. D., Smit, A. B., Gotti, C., et al. (2012) · The FASEB Journal · doi:10.1096/fj.11-198994 · Cited by 44 · cited 6× · see citing works
“Acute nicotine induces increases in the expression of the dendritically targeted dendrin mRNA in PFC of adolescent but not adult animals.”
BackgroundInfluentialSelf-citationAdolescent exposure to nicotine impairs adult serial pattern learning in rats
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Physiological Diversity of Nicotinic Acetylcholine Receptors Expressed by Vertebrate Neurons
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Nicotine causes age-dependent changes in gene expression in the adolescent female rat brain
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DOES SPIKE TIMING‐DEPENDENT SYNAPTIC PLASTICITY UNDERLIE MEMORY FORMATION?
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Flagged first, then by citations
Research works printed but not linked: 1
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Sorted by citations
Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex?
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Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
Adolescent nicotine induces persisting changes in development of neural connectivity.
Smith, R. F., McDonald, C. G., Bergstrom, H. C., Ehlinger, D. G., & Brielmaier, J. M. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.019 · Cited by 120 · see citing works
Fornaro, M., Carvalho, A. F., De Prisco, M., Mondin, A. M., Billeci, M., Selby, P., Iasevoli, F., Berk, M., Castle, D. J., & de Bartolomeis, A. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.11.039 · Cited by 82 · see citing works
Smoking During Adolescence as a Risk Factor for Attention Problems
Treur, J. L., Willemsen, G., Bartels, M., Geels, L. M., van Beek, J. H. D. A., Huppertz, C., van Beijsterveldt, C. E. M., Boomsma, D. I., & Vink, J. M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.06.019 · Cited by 67 · see citing works
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Differential effects of nicotine exposure on the hippocampus across lifespan
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Reynolds, L. M., Faure, P., & Barik, J. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03110-0 · Cited by 26 · see citing works
“Transient changes in nAChR expression following adolescent nicotine exposure have been reviewed elsewhere [44, 53, 113, 114].”
Hoegberg, B. G., Lomazzo, E., Lee, N. H., & Perry, D. C. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.08.015 · Cited by 17 · see citing works
Kutlu, M. G., Zeid, D., Tumolo, J. M., & Gould, T. J. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.06.010 · Cited by 14 · see citing works
- Authors
- Goriounova, N. A., & Mansvelder, H. D.
- Affiliations
- Amsterdam Neuroscience (NL)
- Venue
- Frontiers in Synaptic Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2012
- Volume
- 4
- Pages
- 3-3
- ISSN
- 1663-3563 (ISSN-L)
- PMC
- PMC3410598
- OpenAlex
- W2121084908
- Cited by
- 65
- References
- 109
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 7 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 5
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Synaptic Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (submittedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Vrije Universiteit Amsterdam
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (917.76.360, 912.06.148)
- Seventh Framework Programme (HEALTH‐F2‐2009‐242167, 242167)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- adolescent nicotine exposure, medial prefrontal cortex, synaptic plasticity, metabotropic glutamate receptors, glutamatergic synapses, attention deficits, cognitive impairment, smoking, brain development, long-term synaptic plasticity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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