Cited by 88Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationNeuroscience and Neuropharmacology Research

Upregulation of [3H]methyllycaconitine binding sites following continuous infusion of nicotine, without changes of α7 or α6 subunit mRNA: an autoradiography and in situ hybridization study in rat brain

Mugnaini, Manolo, Tessari, Michela, Tarter, Giorgio, Merlo Pich, Emilio, Chiamulera, Cristiano, Bunnemann, Bernd·2002·European Journal of Neuroscience

Abstract

It is well established that exposure of experimental animals to nicotine results in upregulation of the alpha4beta2-subtype of neuronal nicotinic acetylcholine receptors (nAChRs). The aim of this study was to determine the effect of nicotine on the levels of alpha7-nAChRs in rat brain, for which only partial information is available. Rats were infused with nicotine (3 mg/kg/day) or saline for 2 weeks and their brains processed for receptor autoradiography with [3H]methyllycaconitine (MLA), a radioligand with nanomolar affinity for alpha7-nAChRs. In control rats binding was high in hippocampus, intermediate in cerebral cortex and hypothalamus, and low in striatum, thalamus and cerebellum. There was high correlation between the distribution of [3H]MLA binding sites and alpha7 subunit mRNA (r = 0.816). With respect to saline-treated controls, nicotine-treated rats presented higher [3H]nicotine binding in 11 out of 15 brain regions analysed (average increase 46 +/- 6%). In contrast, only four regions showed greater [3H]MLA binding, among which the ventral tegmental area (VTA) and cingulate cortex (mean increase 32 +/- 3%). No changes in alpha7 mRNA levels were observed after nicotine treatment. Similarly, there was no variation of alpha6 subunit transcript in the VTA, a region which may contain MLA-sensitive (non-alpha7)-alpha6*-nAChRs (Klink et al., 2001). In conclusion, nicotine increased [3H]MLA binding, although to a smaller extent and in a more restricted regional pattern than [3H]nicotine. The enhancement of binding was not paralleled by a significant change of alpha7 and alpha6 subunit transcription. Finally, the present results provide the first anatomical description of the distribution of [3H]MLA binding sites in rat brain.

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Crossref · 10.1046/j.1460-9568.2002.02220.x

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Authors
Mugnaini, M., Tessari, M., Tarter, G., Merlo Pich, E., Chiamulera, C., & Bunnemann, B.
Affiliations
GlaxoSmithKline (Italy) (IT)
Corresponding author
Mugnaini, Manolo
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2002-11
Volume
16
Issue
9
Pages
1633-1646
ISSN
  • 0953-816X (ISSN-L)
  • 1460-9568
OpenAlex
W1983069408
Cited by
88
References
81
Citations by year
2023: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 6 · 2012: 6
FWCI
1.38
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
Federation of European Neuroscience Societies
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
nicotine, alpha7 nicotinic acetylcholine receptor, receptor up-regulation, ventral tegmental area, cingulate cortex, hippocampus, cerebral cortex, hypothalamus, striatum, thalamus, cerebellum, rat brain
MeSH terms
Aconitine, Animals, Autoradiography, Binding Sites, Brain, Nicotine, Receptors, Nicotinic, RNA, Messenger, Up-Regulation, Rats, Wistar, In Situ Hybridization, Nicotinic Agonists, Nicotinic Antagonists, Rats, alpha7 Nicotinic Acetylcholine Receptor

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