Cited by 208Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationPrenatal Substance Exposure Effects

Differential Role of Nicotinic Acetylcholine Receptor Subunits in Physical and Affective Nicotine Withdrawal Signs

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Jackson, K.J., Martin, B.R., Changeux, J.P., Damaj, M.I.·2008·The Journal of Pharmacology and Experimental Therapeutics

Abstract

It has been suggested that the negative effects associated with nicotine withdrawal promote continued tobacco use and contribute to the high relapse rate of smoking behaviors. Thus, it is important to understand the receptor-mediated mechanisms underlying nicotine withdrawal to aid in the development of more successful smoking cessation therapies. The effects of nicotine withdrawal are mediated through nicotinic acetylcholine receptors (nAChRs); however, the role of nAChRs in nicotine withdrawal remains unclear. Therefore, we used mecamylamine-precipitated, spontaneous, and conditioned place aversion (CPA) withdrawal models to measure physical and affective signs of nicotine withdrawal in various nAChR knockout (KO) mice. beta2, alpha7, and alpha5 nAChR KO mice were chronically exposed to nicotine through surgically implanted osmotic minipumps. Our results show a loss of anxiety-related behavior and a loss of aversion in the CPA model in beta2 KO mice, whereas alpha7 and alpha5 KO mice displayed a loss of nicotine withdrawal-induced hyperalgesia and a reduction in somatic signs, respectively. These results suggest that beta2-containing nAChRs are involved in the affective signs of nicotine withdrawal, whereas non-beta2-containing nAChRs are more closely associated with physical signs of nicotine withdrawal; thus, the nAChR subtype composition may play an important role in the involvement of specific subtypes in nicotine withdrawal.

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Crossref · 10.1124/jpet.107.132977

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  • α5 knockout mice show neither physical signs of spontaneous or mecamylamine-precipitated nicotine withdrawal nor withdrawal-induced hyperalgesia.

    “α5 KO mice do not display physical symptoms associated with both spontaneous and mecamylamine-precipitated nicotine withdrawal (Salas et al. 2009) nor withdrawal-induced hyperalgesia (Jackson et al. 2008).”

    From Nicotine Withdrawal (2015) · cites this paper as Jackson et al. 2008

    Jackson et al.’s Results (‘Role of the α5 nAChR Subunit in Precipitated Nicotine Withdrawal’) report significant withdrawal-induced hyperalgesia in α5 knockout mice, contrary to the part of the sentence cited to Jackson et al. The statement about spontaneous and mecamylamine-precipitated physical symptoms is cited to Salas et al. (2009), not to this source. (LLM, conf=0.95)

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  • The β2*-subtype does not play a critical role in the physical symptoms of nicotine withdrawal.

    “This is consistent with the preclinical literature suggesting that the β2*-subtype does not play a critical role in the physical symptoms of nicotine withdrawal33, 76.”
  • The α5 null mutation does not appear to affect affective withdrawal symptoms such as conditioned place aversion.

    “The α5 null mutation does not appear to influence affective symptoms such as withdrawal-induced CPA (Jackson et al. 2008).”

    From Nicotine Withdrawal (2015) · cites this paper as Jackson et al. 2008

  • β2 knockout mice do not show the anxiety-related behaviors normally associated with withdrawal from chronic nicotine.

    “However, the mutant mice do not exhibit anxiety-related behaviors normally associated with withdrawal from chronic nicotine exposure (Jackson et al. 2008).”

    From Nicotine Withdrawal (2015) · cites this paper as Jackson et al. 2008

  • Absence of α2, α5, or β4 nAChR subunits abolishes somatic manifestations of nicotine withdrawal.

    “The MHb/IPN express nAChRs comprising the α2 (IPN), α5, and/or β4 nAChR subunits and absence of any one of those nAChR subunits abolishes the somatic manifestations of nicotine withdrawal [11, 81, 170].”

    From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [170]

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Authors
Jackson, K. J., Martin, B. R., Changeux, J. P., & Damaj, M. I.
Affiliations
Virginia Commonwealth University (US)
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2008-04
Volume
325
Issue
1
Pages
302-312
ISSN
0022-3565 (ISSN-L)
OpenAlex
W1965573444
Cited by
208
References
38
Citations by year
2026: 2 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 9 · 2017: 11 · 2016: 9 · 2015: 16 · 2014: 20 · 2013: 18 · 2012: 14
FWCI
7.81
Type
journal article
Language
en
Open access
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Drug Abuse (R01DA012610, DA 05274, DA-12610, P50DA005274)
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
nicotinic acetylcholine receptors, nicotine withdrawal, beta2 nAChR, alpha7 nAChR, conditioned place aversion, anxiety, hyperalgesia, somatic withdrawal signs, smoking cessation
MeSH terms
Animals, Conditioning, Psychological, Nicotine, Receptors, Nicotinic, Substance Withdrawal Syndrome, Mice, Knockout, Protein Subunits, Mice, alpha7 Nicotinic Acetylcholine Receptor

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