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Cited by 36Smoking Behavior and CessationNeuropeptides and Animal PhysiologyNicotinic Acetylcholine Receptors Study

Neuropeptide systems and new treatments for nicotine addiction

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Bruijnzeel, Adriaan W.·2017·Psychopharmacology
DOI 10.1007/s00213-016-4513-5PMC PMC5420481
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Abstract

Rationale The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. Objectives The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking. Results The reviewed studies indicate that several drugs that target neuropeptide systems diminish the rewarding effects of nicotine by preventing the activation of dopaminergic systems. Other peptide-based drugs diminish the hyperactivity of brain stress systems and diminish withdrawal-associated symptom severity. Blockade of hypocretin-1 and nociceptin receptors and stimulation of galanin and neurotensin receptors diminishes the rewarding effects of nicotine. Both corticotropin-releasing factor type 1 and kappa-opioid receptor antagonists diminish dysphoria and anxiety-like behavior associated with nicotine withdrawal and inhibit stress-induced reinstatement of nicotine seeking. Furthermore, blockade of vasopressin 1b receptors diminishes dysphoria during nicotine withdrawal, and melanocortin 4 receptor blockade prevents stress-induced reinstatement of nicotine seeking. The role of neuropeptide systems in nicotine-primed and cue-induced reinstatement is largely unexplored, but there is evidence for a role of hypocretin-1 receptors in cue-induced reinstatement of nicotine seeking. Conclusion Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience.

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  • Nicotine influences the central nervous system by modulating appetite-regulating peptides such as GLP-1 and hypocretin-1, which play crucial roles in hunger and satiety signals.

    “Furthermore, nicotine also influences the central nervous system by modulating appetite-regulating peptides such as glucagon-like peptide- 1 (GLP-1) and hypocretin-1, which play crucial roles in hunger and satiety signals [21, 22].”

    From Smoking and its impact on eating behavior: A review (2026) · cites this paper as [22]

    Section 7 reports that acute nicotine increases activity in hypocretin neurons, and Section 6 says hypocretins regulate feeding. The paper does not establish that nicotine modulates GLP-1 or that its effects on these peptides govern hunger and satiety signals; its discussion of hypocretin focuses on nicotine reward and seeking. The indexed copy provides no page numbers for these passages. (LLM, conf=0.86)

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Authors
Bruijnzeel, A. W.
Affiliations
University of Florida (US)
Corresponding author
Bruijnzeel, Adriaan W.
ORCID
Bruijnzeel, Adriaan W.
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2016-12-28
Volume
234
Issue
9-10
Pages
1419-1437
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-016-4513-5
PMC
PMC5420481
OpenAlex
W2565256373
Cited by
36
References
18
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 2
FWCI
0.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (DA042530)
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
nicotine dependence, neuropeptide systems, nicotine withdrawal, relapse, nociceptin receptor, galanin receptors, neurotensin receptor, kappa opioid receptor, melanocortin-4 receptor, stress resilience, smoking initiation, dysphoria, anxiety
MeSH terms
Animals, Anxiety, Corticotropin-Releasing Hormone, Humans, Neuropeptides, Nicotine, Self Administration, Substance Withdrawal Syndrome, Tobacco Use Disorder, Smoking Cessation, Treatment Outcome, Receptors, Opioid, kappa

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