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
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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a7 nAChRs do not upregulate to the same degree as heteromeric nAChRs after long-term nicotine treatment.
“This outcome was expected, because a7 nAChRs do not upregulate to the same degree as heteromeric nAChRs after long-term nicotine treatment (Mugnaini et al., 2002).”
From Activation of α4β2*/α6β2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors (2014) · cites this paper as Mugnaini et al., 2002
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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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