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SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats
Abstract
The central CB(1) cannabinoid receptor has recently been implicated in brain reward function. In the present study we evaluated first the effects of the selective CB(1) receptor antagonist, SR141716, on the motivational effects of nicotine in the rat. Administration of SR141716 (0.3 and 1 mg/kg) decreased nicotine self-administration (0.03 mg/kg/injection). SR141716 (0.3-3 mg/kg) neither substituted for nicotine nor antagonized the nicotine cue in a nicotine discrimination procedure, but dose-dependently (0.01-1 mg/kg) antagonized the substitution of nicotine for D-amphetamine, in rats trained to discriminate D-amphetamine. Secondly, using brain microdialysis, SR141716 (1-3 mg/kg) blocked nicotine-induced dopamine release in the shell of the nucleus accumbens (NAc) and the bed nucleus of the stria terminalis. To investigate whether SR141716 would block the dopamine-releasing effects of another drug of abuse, we extended the neurochemical study to the effect of ethanol, consumption of which in rodents is reduced by SR141716. Dopamine release induced by ethanol in the NAc was also reduced by SR141716 (3 mg/kg). These results suggest that activation of the endogenous cannabinoid system may participate in the motivational and dopamine-releasing effects of nicotine and ethanol. Thus, SR141716 may be effective in reduction of alcohol consumption, as previously suggested, and as an aid for smoking cessation.
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“Vaccination of rats against nicotine (or passive immunization with nicotine-specific IgG to simulate vaccination) attenuates physiological and behavioral responses to nicotine (134).”
From Tobacco addiction (2008) · cites this paper as [134]
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Metadata
- Authors
- Cohen, C., Perrault, G., Voltz, C., Steinberg, R., & Soubrié, P.
- Affiliations
- Sanofi (France) (FR)
- Corresponding author
- Cohen, C.
- Venue
- Behavioural Pharmacology
- Published
- 2002-09
- Volume
- 13
- Issue
- 5
- Pages
- 451-463
- ISSN
- 0955-8810 (ISSN-L)
- OpenAlex
- W2001109168
- Cited by
- 396
- References
- 77
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 4 · 2023: 11 · 2022: 9 · 2021: 7 · 2020: 13 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 20 · 2015: 14 · 2014: 9 · 2013: 19 · 2012: 16
- FWCI
- 16.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- 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
- SR141716, nicotine self-administration, dopamine release, nucleus accumbens shell, bed nucleus of the stria terminalis, endocannabinoid system, drug reward, alcohol consumption reduction, smoking cessation
- MeSH terms
- Rimonabant, Ethanol, Animals, Brain Chemistry, Central Nervous System Depressants, Discrimination Learning, Dopamine, Extracellular Space, Male, Motivation, Nicotine, Nucleus Accumbens, Piperidines, Pyrazoles, Receptors, Drug, Reinforcement, Psychology, Self Administration, Rats, Sprague-Dawley, Rats, Wistar, Microdialysis, Nicotinic Agonists, Nicotinic Antagonists, Receptors, Cannabinoid, Rats
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