Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity
Abstract
Nicotine is a major component of tobacco smoke contributing to the initiation and persistence of the harmful tobacco habit in human smokers. The reinforcing effects of nicotine likely arise through its ability to stimulate brain circuitry mediating the detection and experiencing of natural rewards. Nevertheless, remarkably little is known concerning the acute or long-lasting actions of nicotine on brain reward systems in vivo. Here, we investigated the effects of intravenously self-administered nicotine (0.03 mg/kg/infusion, free base) on the sensitivity of brain reward systems, reflected in alterations of intracranial self-stimulation (ICSS) thresholds in rats. Rats self-administered nicotine during 1 or 12 h daily sessions, with reward thresholds assessed 1 h before and 15 min after each self-administration session. Control rats remained nicotine naïve throughout. Nicotine self-administration increased the sensitivity of brain reward systems, detected by post-nicotine lowering of reward thresholds in 1 and 12 h rats. This nicotine-enhanced sensitivity of reward systems was reversed by the high-affinity nicotinic receptor antagonist dihydro-beta-erythroidine (DHbetaE; 3 mg/kg). Surprisingly, nicotine-induced excitation of reward systems persisted for at least 36 days after nicotine self-administration had ceased. Overall, these data demonstrate that rats can voluntarily consume quantities of nicotine sufficient to increase the sensitivity of brain reward systems, an action likely crucial in establishing and maintaining the nicotine habit. Moreover, self-administered nicotine resets the sensitivity of reward systems to a new increased level, thereby imprinting an indelible 'memory' of its effects in reward systems, an action that so far appears unique to nicotine among drugs of abuse.
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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 [38]
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- Authors
- Kenny, P. J., & Markou, A.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Markou, Athina
- ORCID
- Kenny, Paul J
- Venue
- Neuropsychopharmacology
- Published
- 2005-09-28
- Volume
- 31
- Issue
- 6
- Pages
- 1203-1211
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2078241277
- Cited by
- 261
- References
- 48
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 17 · 2020: 26 · 2019: 8 · 2018: 14 · 2017: 8 · 2016: 15 · 2015: 15 · 2014: 21 · 2013: 10 · 2012: 19
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotine, self-administration, brain reward system, reward sensitivity, intracranial self-stimulation, nicotinic acetylcholine receptors, dihydro-beta-erythroidine, nicotine dependence
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Brain, Dihydro-beta-Erythroidine, Male, Nicotine, Reward, Self Administration, Substance Withdrawal Syndrome, Time Factors, Rats, Wistar, Nicotinic Agonists, Rats
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