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Cited by 40Nicotinic Acetylcholine Receptors StudySmoking Behavior and CessationNeurotransmitter Receptor Influence on Behavior

Role of α7- and β4-Containing Nicotinic Acetylcholine Receptors in the Affective and Somatic Aspects of Nicotine Withdrawal: Studies in Knockout Mice

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Stoker, Astrid K., Olivier, Berend, Markou, Athina·2012·Behavior Genetics
DOI 10.1007/s10519-011-9511-0PMC PMC3304011
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Abstract

To assess which nicotinic acetylcholine receptors (nAChRs) are involved in the aversive aspects of nicotine withdrawal, brain reward function and the somatic signs of nicotine withdrawal were assessed in mice that lack α7 and β4 nAChR subunits. Brain reward function was assessed with the intracranial self-stimulation (ICSS) procedure, in which elevations in ICSS thresholds reflect an anhedonic mood state. At 3-6 h of spontaneous nicotine/saline withdrawal, thresholds were elevated in nicotine-withdrawing α7(+/+) and β4(+/+), but not α7(-/-) or β4(-/-), mice compared with saline-withdrawing mice, indicating a delay in the onset of withdrawal in the knockout mice. From 8 to 100 h of withdrawal, thresholds in α7(+/+) and α7(-/-) mice were equally elevated, whereas thresholds in β4(+/+) and β4(-/-) mice returned to baseline levels. Somatic signs were attenuated in nicotine-withdrawing β4(-/-), but not α7(-/-), mice. Administration of a low dose of the nAChR antagonist mecamylamine induced threshold elevations in α7(-/-), but not α7(+/+), mice, whereas the highest dose tested only elevated thresholds in α7(+/+) mice. Mecamylamine-induced threshold elevations were similar in β4(-/-) and β4(+/+) mice. In conclusion, null mutation of the α7 and β4 nAChR subunits resulted in a delayed onset of the anhedonic aspects of the spontaneous nicotine withdrawal syndrome. Previous findings of attenuated somatic signs of nicotine withdrawal in β4(-/-), but not α7(-/-), mice were confirmed in the present study, indicating an important role for β4-containing nAChRs in the somatic signs of nicotine withdrawal. The mecamylamine-precipitated withdrawal data suggest that compensatory adaptations may occur in constitutive α7(-/-) mice or that mecamylamine may interact with other receptors besides nAChRs in these mice. In summary, the present results indicate an important role for α7 and β4-containing nAChRs in the anhedonic or somatic signs of nicotine withdrawal.

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  • β4 knockout mice undergoing spontaneous withdrawal from chronic nicotine show similar absence of somatic withdrawal signs.

    “Similar results were found for β4 KO mice undergoing spontaneous withdrawal from chronic nicotine administration (Stoker et al. 2012).”

    From Nicotine Withdrawal (2015) · cites this paper as Stoker et al. 2012

    The Results (Spontaneous nicotine withdrawal; page not provided) report no increase in somatic signs in β4 knockout mice after withdrawal from 40 mg/kg/day nicotine. At 80 mg/kg/day, however, signs were attenuated compared with wildtype mice but significantly higher than in saline-treated knockout mice. The claim's unqualified absence of somatic withdrawal signs is therefore too broad. (LLM, conf=0.88)

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  • Lack of α7 delays withdrawal symptoms rather than eliminating them.

    “When the anhedonic affective state was evaluated between 8 and 100 h after nicotine withdrawal, ICSS thresholds were equally elevated in α7 WT and null littermates, indicating that a lack of α7 nAChR subunits delays, rather than abolishes, withdrawal symptoms.”

    From Nicotine Withdrawal (2015) · cites this paper as Stoker et al. 2012

  • β4 knockout mice do not show anhedonia-like symptoms during withdrawal, as indicated by unchanged intracranial self-stimulation thresholds.

    “In addition, β4 KO mice do not display anhedonia-like symptoms during withdrawal, as identified by unchanged intracranial self-stimulation thresholds (Stoker et al. 2012).”

    From Nicotine Withdrawal (2015) · cites this paper as Stoker et al. 2012

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  1. American Psychiatric Association Diagnostic and statistical manual of mental disorders, 4th edn, text revision 2000 American Psychiatric Press Washington DC

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Authors
Stoker, A. K., Olivier, B., & Markou, A.
Affiliations
  • Utrecht University (NL)
  • University of California San Diego (US)
Corresponding author
Markou, Athina
ORCID
Olivier, Berend
Venue
Behavior Genetics
Publisher
Springer Science and Business Media LLC
Published
2011-10-19
Volume
42
Issue
3
Pages
423-436
ISSN
  • 0001-8244 (ISSN-L)
  • 1573-3297
DOI
10.1007/s10519-011-9511-0
PMC
PMC3304011
OpenAlex
W2077930990
Cited by
40
References
85
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 2
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Behavior Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Drug Abuse (P30DA015663, R01DA023209)
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
nicotinic acetylcholine receptors, alpha7 nAChR, nicotine withdrawal, anhedonia, somatic withdrawal signs, brain reward, intracranial self-stimulation, mecamylamine, knockout mice, receptor knockout
MeSH terms
Affect, Animals, Behavior, Animal, Drug Implants, Electrodes, Implanted, Mecamylamine, Mice, Inbred C57BL, Nerve Tissue Proteins, Nicotine, Receptors, Nicotinic, Self Stimulation, Substance Withdrawal Syndrome, Mice, Knockout, Nicotinic Agonists, Nicotinic Antagonists, Mice, alpha7 Nicotinic Acetylcholine Receptor

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