Nicotine-associated cues maintain nicotine-seeking behavior in rats several weeks after nicotine withdrawal: reversal by the cannabinoid (CB1) receptor antagonist, rimonabant (SR141716)
Abstract
Conditioned stimuli are important for nicotine dependence and may trigger craving and relapse after prolonged nicotine abstinence. However, little is known about the pharmacology of this process. Among the systems that have been shown to play a role in drug-seeking behavior is the endocannabinoid transmission. Therefore, the present study examined the resistance to extinction of drug-seeking behavior elicited by nicotine-associated environmental stimuli and the effects of the selective CB1 cannabinoid antagonist rimonabant (SR141716) on the reinforcing effects of nicotine-related stimuli. Rats were trained to self-administer nicotine (0.03 mg/kg/injection, i.v.) under conditions in which responding was reinforced jointly by response-contingent nicotine injections and stimuli (light and tone). After self-administration acquisition, nicotine was withdrawn and lever pressing was only reinforced by contingent presentation of the audiovisual stimuli. Under such a condition, responding persisted for 3 months, following which nonpresentation of the cues produced a progressive extinction of responding. As expected, rats trained to lever-press for saline injections paired with the audiovisual stimuli did not acquire the self-administration. These findings indicate that the cues required learned association with nicotine to acquire reinforcing properties and to function as conditioned reinforcers. When administered 1 month following nicotine withdrawal, rimonabant (1 mg/kg, i.p.) decreased conditioned behavior. These results showing the persistence of a nicotine-conditioned behavior are congruent with the role of nicotine-related environmental stimuli in nicotine craving in abstinent smokers. Rimonabant, which has been shown previously to reduce nicotine self-administration, may be effective not only as an aid for smoking cessation but also in the maintenance of abstinence.
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Vaccinated rats have demonstrated reduced nicotine-induced dopamine release in the brain.
“In addition, vaccinated rats have also demonstrated reduced nicotine-induced dopamine release in the brain (135).”
From Tobacco addiction (2008) · cites this paper as [135]
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- Authors
- Cohen, C., Perrault, G., Griebel, G., & Soubrié, P.
- Affiliations
- Sanofi (France) (FR)
- Corresponding author
- Cohen, Caroline
- ORCID
- Griebel, Guy
- Venue
- Neuropsychopharmacology
- Published
- 2004-08-04
- Volume
- 30
- Issue
- 1
- Pages
- 145-155
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2070212982
- Cited by
- 251
- References
- 51
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 11 · 2016: 11 · 2015: 10 · 2014: 10 · 2013: 8 · 2012: 15
- FWCI
- 16.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- nicotine, nicotine withdrawal, conditioned cues, rimonabant, endocannabinoid system, extinction resistance, conditioned reinforcement, nicotine self-administration, smoking cessation, nicotine dependence, relapse
- MeSH terms
- Rimonabant, Acoustic Stimulation, Animals, Cues, Dopamine, Environment, Extinction, Psychological, Light, Male, Motivation, Motor Activity, Synaptic Transmission, Nicotine, Piperidines, Pyrazoles, Self Administration, Substance Withdrawal Syndrome, Tobacco Use Disorder, Rats, Sprague-Dawley, Nicotinic Agonists, Receptor, Cannabinoid, CB1, Rats
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