Cited by 42Nicotinic Acetylcholine Receptors StudyNeuroscience and Neuropharmacology ResearchSmoking Behavior and Cessation

Developmental regulation of nicotinic acetylcholine receptor‐mediated [3H]norepinephrine release from rat cerebellum

O'Leary, K. T., Leslie, F. M.·2003·Journal of Neurochemistry

Abstract

Presynaptic modulation of synaptic transmission is the primary function of central nicotinic acetylcholine receptors (nAChRs) in developing and adult brain. nAChR activation regulates release of various neurotransmitters, including norepinephrine (NA). Given evidence that NA may serve a critical functional role in cerebellar development, we have undertaken studies to determine whether nAChRs modulate NA release in developing cerebellum. In vitro experiments using cerebellar slices examined the effects of nAChR stimulation on release of radiolabeled NA ([3H]NA). Our data indicate the presence of functional nAChRs on NA terminals in immature cerebellum and subsequent developmental regulation of receptor properties. During postnatal week one, the maximally effective dose of nicotine released 35.0 +/- 1.2% of cerebellar [3H]NA stores. There was a subsequent decline in maximal nicotine-stimulated NA release until postnatal day 30, when Emax values were statistically indistinguishable from adult. Although the efficacy of nicotine changed substantially throughout development, EC50 values did not differ significantly (EC50 = 4.4-12.0 micro m). Pharmacological analysis indicated that this developmental shift in maximum nicotine effect reflects a change in the properties of the nAChRs. These data support recent findings of a possible functional role of nAChRs in regulating cerebellar ontogeny, and provides further support for the role of NA as a neurotrophic factor during development.

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Crossref · 10.1046/j.1471-4159.2003.01575.x

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Authors
O'Leary, K. T., & Leslie, F. M.
Affiliations
University of California, Irvine (US)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2003-02-07
Volume
84
Issue
5
Pages
952-959
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W1498625688
Cited by
42
References
74
Citations by year
2026: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2018: 1 · 2016: 2 · 2014: 1 · 2013: 3 · 2012: 3
FWCI
1.50
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Electronics and Telecommunications Research Institute
  • U.S. Public Health Service
  • National Institute on Drug Abuse (DA-10612, P50DA013332, R01DA010612, DA 13332)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords
nicotinic acetylcholine receptors, noradrenaline release, cerebellum, cerebellar development, presynaptic modulation, nicotine, postnatal development, receptor maturation, neurotrophic factors, synaptic transmission
MeSH terms
Age Factors, Aging, Animals, Animals, Newborn, Cerebellum, Dose-Response Relationship, Drug, Female, Fluoxetine, Male, Nicotine, Norepinephrine, Receptors, Nicotinic, Tritium, Rats, Sprague-Dawley, Gene Expression Regulation, Developmental, Nicotinic Agonists, Nicotinic Antagonists, Symporters, Norepinephrine Plasma Membrane Transport Proteins, Rats, In Vitro Techniques

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