Cited by 61Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationNeurotransmitter Receptor Influence on Behavior

Addiction‐related neuroadaptations following chronic nicotine exposure

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Wills, Lauren, Kenny, Paul J.·2021·Journal of Neurochemistry

Abstract

The addiction‐relevant molecular, cellular, and behavioral actions of nicotine are derived from its stimulatory effects on neuronal nicotinic acetylcholine receptors (nAChRs) in the central nervous system. nAChRs expressed by dopamine‐containing neurons in the ventral midbrain, most notably in the ventral tegmental area (VTA), contribute to the reward‐enhancing properties of nicotine that motivate the use of tobacco products. nAChRs are also expressed by neurons in brain circuits that regulate aversion. In particular, nAChRs expressed by neurons in the medial habenula (mHb) and the interpeduncular nucleus (IPn) to which the mHb almost exclusively projects regulate the “set‐point” for nicotine aversion and control nicotine intake. Different nAChR subtypes are expressed in brain reward and aversion circuits and nicotine intake is titrated to maximally engage reward‐enhancing nAChRs while minimizing the recruitment of aversion‐promoting nAChRs. With repeated exposure to nicotine, reward‐ and aversion‐related nAChRs and the brain circuits in which they are expressed undergo adaptations that influence whether tobacco use will transition from occasional to habitual. Genetic variation that influences the sensitivity of addiction‐relevant brain circuits to the actions of nicotine also influence the propensity to develop habitual tobacco use. Here, we review some of the key advances in our understanding of the mechanisms by which nicotine acts on brain reward and aversion circuits and the adaptations that occur in these circuits that may drive addiction to nicotine‐containing tobacco products. image

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  • By desensitizing nicotine receptors, nicotine can inhibit negative aversive states.

    “By desensitizing nicotine receptors, nicotine can inhibit negative aversive states 42 .”

    From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [42]

    The Introduction section on nAChR upregulation reports that nicotine desensitizes nicotinic receptors. The section on low-affinity nAChRs reports reduced aversive responses when certain receptor subunits are deficient. Neither passage establishes that nicotine inhibits aversive states by desensitizing those receptors; the claimed mechanism is unsupported. (LLM, conf=0.82)

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Authors
Wills, L., & Kenny, P. J.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Kenny, Paul J.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2021-06
Volume
157
Issue
5
Pages
1652-1673
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W3137382578
Cited by
61
References
333
Citations by year
2026: 10 · 2025: 6 · 2024: 14 · 2023: 18 · 2022: 7 · 2021: 6
FWCI
1.18
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
National Institute on Drug Abuse (DA020686, DA045649)
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 › Neurotransmitter Receptor Influence on Behavior
Keywords
nicotine dependence, nicotine aversion, nicotinic acetylcholine receptors, ventral tegmental area, medial habenula, interpeduncular nucleus, nicotine reward, neural adaptation
MeSH terms
Adaptation, Physiological, Animals, Dopamine, Humans, Nicotine, Receptors, Nicotinic, Reward, Tobacco Use Disorder

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