Administration of nicotine to adolescent rats evokes regionally selective upregulation of CNS α7 nicotinic acetylcholine receptors
Abstract
Alpha 7 Nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis, synaptogenesis and synaptic plasticity, and are therefore targets for developmental neurotoxicants. We administered nicotine to adolescent rats and evaluated the effects on alpha 7 nAChRs in the striatum, brainstem and cerebellum. During the period of nicotine administration (30-47.5 days of age), nicotine elicited alpha 7 nAChR upregulation with a regional hierarchy of striatum>brainstem>cerebellum. Values returned to normal or became slightly subnormal almost immediately after the cessation of treatment (50 days of age) with no further changes through 75 days of age. The temporal and regional patterns of the effects on alpha 7 nAChRs were distinct from those reported earlier for the alpha 4 beta 2 subtype, and neither adult nor fetal/neonatal administration upregulates the alpha 7 subtype in the striatum. Targeting of the striatum is thus unique to nicotine exposure during adolescence and parallels earlier work showing regionally selective effects of this treatment on synaptic signaling. We obtained preliminary evidence for nicotine-induced oxidative stress as a potential contributory mechanism. The present findings reinforce the concept of biologically distinct effects of nicotine in the adolescent brain and provide evidence for a mechanistic involvement of alpha 7 nAChRs in its unique effects during this developmental period.
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Upregulation of α7-containing nAChRs in the striatum, brainstem, and cerebellum was apparent only transiently.
“while an upregulation of α7- containing NAChRs in the striatum, brainstem, and cerebellum was apparent only transiently [116].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [116]
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- Authors
- Slotkin, T. A., Cousins, M. M., & Seidler, F. J.
- Affiliations
- Duke University (US)
- Corresponding author
- Slotkin, Theodore A.
- ORCID
- Slotkin, Theodore A.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2004-12
- Volume
- 1030
- Issue
- 1
- Pages
- 159-163
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1988177534
- Cited by
- 40
- References
- 38
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- nicotine, alpha7 nicotinic acetylcholine receptor, adolescent brain development, striatum, brainstem, cerebellum, developmental neurotoxicity, oxidative stress, synaptic plasticity, receptor desensitization
- MeSH terms
- Age Factors, Animals, Brain, Brain Stem, Cerebellum, Corpus Striatum, Nicotine, Receptors, Nicotinic, Sexual Maturation, Up-Regulation, Rats, Sprague-Dawley, Nicotinic Agonists, Rats, alpha7 Nicotinic Acetylcholine Receptor
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