Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat
Abstract
Rationale Bupropion is an atypical antidepressant and the only non-nicotine-based therapy approved for smoking cessation. Its use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation.Objectives We assessed the effects of bupropion on brain reward function under baseline conditions and subsequent to withdrawal from chronic nicotine administration in rats.Methods A discrete-trial intracranial self-stimulation paradigm procedure was used that provides one with current intensity thresholds, a measure of reward in rats under baseline conditions and subsequent to withdrawal from chronic nicotine (3.16 mg/kg per day for 7 days via osmotic minipump). Somatic signs were recorded based on a checklist of nicotine abstinence signs in animals withdrawn from nicotine.Results Bupropion (10-60 mg/kg) dose-dependently lowered reward thresholds in non-withdrawing subjects indicating an increase in reward. Interestingly, a sub-effective dose of bupropion (5 mg/kg) blocked completely the threshold lowering effects of acute nicotine (0.25 mg/kg). Animals withdrawn from chronic nicotine exhibited increases in somatic signs of withdrawal and elevated brain reward thresholds, which is indicative of "diminished interest or pleasure" (i.e. anhedonia) in the rewarding stimuli. Bupropion (10-40 mg/kg) reversed both the reward deficit and the somatic signs, with the highest dose (40 mg/kg) inducing a protracted reversal of the threshold elevation.Conclusions Bupropion acts on multiple levels to alter brain reward circuits influenced by nicotine, in addition to reducing the expression of somatic signs of withdrawal. First, bupropion, unlike other antidepressants, increases brain reward function under baseline conditions in non-withdrawing subjects. Second, at low doses bupropion blocks the rewarding effects of nicotine. Third, bupropion reverses the negative affective aspects of nicotine withdrawal. Such actions are likely to act in concert to mediate the unique anti-smoking properties of bupropion.
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Varenicline's beneficial effects on affect during abstinence are consistent with preclinical evidence for the role of α4β2 nicotinic acetylcholine receptors in nicotine's effect on hedonic state.
“The beneficial effects of varenicline on affect during abstinence are consistent with preclinical evidence for the role of α4β2 nAChRs in nicotine’s effect on hedonic state.”
From Varenicline improves mood and cognition during smoking abstinence (2009) · cites this paper as [37]
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- Authors
- Cryan, J. F., Bruijnzeel, A. W., Skjei, K. L., & Markou, A.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Markou, Athina
- Venue
- Psychopharmacology
- Published
- 2003-07-01
- Volume
- 168
- Issue
- 3
- Pages
- 347-358
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W1986183173
- Cited by
- 223
- References
- 79
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 7 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 9 · 2016: 8 · 2015: 15 · 2014: 12 · 2013: 2 · 2012: 9
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 62527, R01MH062527)
- National Institute on Drug Abuse (DA 11946, R56DA011946)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- bupropion, nicotine withdrawal, intracranial self-stimulation, anhedonia, smoking cessation, nicotine reward, somatic withdrawal signs, antidepressants, nicotine antagonism
- MeSH terms
- Animals, Brain, Drug Administration Schedule, Electric Stimulation, Male, Nicotine, Receptors, Nicotinic, Reward, Substance Withdrawal Syndrome, Bupropion, Rats, Wistar, Antidepressive Agents, Second-Generation, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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