Dramatic decreases in brain reward function during nicotine withdrawal
Abstract
Tobacco smoking is a worldwide public health problem. In the United States alone, over 400,000 deaths and $50 billion in medical costs annually are directly attributed to smoking. Accumulated evidence indicates that nicotine is the component of tobacco smoke that leads to addiction, but the means by which nicotine produces addiction remain unclear. Nicotine is less effective as a positive reinforcer than other drugs of abuse in non-dependent animals. Nevertheless, nicotine-withdrawal symptoms, including depressed mood, anxiety, irritability and craving in dependent subjects may contribute to the addictive liability of nicotine. We show here that spontaneous nicotine withdrawal in rats resulted in a significant decrease in brain reward function, as measured by elevations in brain reward thresholds, which persisted for four days. Further, systemic injections of a competitive nicotinic-receptor antagonist led to a dose-dependent increase in brain reward thresholds in chronic nicotine-treated rats. The decreased function in brain reward systems during nicotine withdrawal is comparable in magnitude and duration to that of other major drugs of abuse, and may constitute an important motivational factor that contributes to craving, relapse and continued tobacco consumption in humans.
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Rats undergoing spontaneous withdrawal from chronic nicotine show a dramatic increase in ICSS reward thresholds.
“Rats undergoing spontaneous withdrawal from chronic nicotine treatment show a dramatic increase in reward thresholds [167].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [167]
Nicotine withdrawal is associated with increases in reward thresholds, suggesting that these effects are likely to initiate, rather than maintain addiction.
“However, nicotine withdrawal is also associated with increases in reward thresholds (Epping-Jordan et al., 1998) suggesting that these effects are likely to initiate, rather than maintain addiction.”
From An application of the stress-diathesis model: A review about the association between smoking tobacco, smoking cessation, and mental health (2023) · cites this paper as Epping-Jordan et al., 1998
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- Authors
- Epping-Jordan, M. P., Watkins, S. S., Koob, G. F., & Markou, A.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Markou, Athina
- Venue
- Nature
- Published
- 1998-05
- Volume
- 393
- Issue
- 6680
- Pages
- 76-79
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1516172865
- Cited by
- 674
- References
- 31
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 9 · 2023: 10 · 2022: 8 · 2021: 23 · 2020: 11 · 2019: 25 · 2018: 25 · 2017: 22 · 2016: 24 · 2015: 25 · 2014: 29 · 2013: 23 · 2012: 29
- FWCI
- 14.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine withdrawal, nicotine dependence, smoking, reward threshold, nicotinic antagonists, craving, relapse
- MeSH terms
- Animals, Brain, Dihydro-beta-Erythroidine, Disease Models, Animal, Male, Motivation, Nicotine, Reward, Self Stimulation, Sensory Thresholds, Substance Withdrawal Syndrome, Infusion Pumps, Implantable, Rats, Wistar, Nicotinic Antagonists, Rats
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