The CB1Neutral Antagonist AM4113 Retains the Therapeutic Efficacy of the Inverse Agonist Rimonabant for Nicotine Dependence and Weight Loss with Better Psychiatric Tolerability
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BACKGROUND: neutral antagonist AM4113 on the abuse-related effects of nicotine and its effects on anxiety and depressive-like behavior in rats. METHODS: Rats were trained to self-administer nicotine under a fixed-ratio 5 or progressive-ratio schedules of reinforcement. A control group was trained to self-administer food. The acute/chronic effects of AM4113 pretreatment were evaluated on nicotine taking, motivation for nicotine, and cue-, nicotine priming- and yohimbine-induced reinstatement of nicotine-seeking. The effects of AM4113 in the basal firing and bursting activity of midbrain dopamine neurons were evaluated in a separate group of animals treated with nicotine. Anxiety/depression-like effects of AM4113 and rimonabant were evaluated 24h after chronic (21 days) pretreatment (0, 1, 3, and 10mg/kg, 1/d). RESULTS: AM4113 significantly attenuated nicotine taking, motivation for nicotine, as well as cue-, priming- and stress-induced reinstatement of nicotine-seeking behavior. These effects were accompanied by a decrease of the firing and burst rates in the ventral tegmental area dopamine neurons in response to nicotine. On the other hand, AM4113 pretreatment did not have effects on operant responding for food. Importantly, AM4113 did not have effects on anxiety and showed antidepressant-like effects. CONCLUSION: Our results indicate that AM4113 could be a promising therapeutic option for the prevention of relapse to nicotine-seeking while lacking anxiety/depression-like side effects.
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A neutral CB1 antagonist (AM4113) may retain the therapeutic potential of inverse agonists, possibly without the neuropsychiatric side effects.
“The recent report that a neutral CB1 antagonist (AM4113) may retain the therapeutic potential of inverse agonists 66, 67, possibly without the neuropsychiatric side effects 67”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [67]
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- Authors
- Gueye, A. B., Pryslawsky, Y., Trigo, J. M., Poulia, N., Delis, F., Antoniou, K., Loureiro, M., Laviolette, S. R., Vemuri, K., Makriyannis, A., & Le Foll, B.
- Affiliations
- Western University (CA)
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-04
- Volume
- 19
- Issue
- 12
- Pages
- pyw068
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC5203757
- OpenAlex
- W2496570843
- Cited by
- 74
- References
- 56
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 9 · 2023: 5 · 2022: 7 · 2021: 11 · 2020: 6 · 2019: 7 · 2018: 11 · 2017: 10 · 2016: 1
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- NIDA
- NIH
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Keywords
- rimonabant, nicotine dependence, nicotine self-administration, cue-induced relapse, yohimbine, ventral tegmental area dopamine neurons, anxiety-like behavior, depression-like behavior, weight loss
- MeSH terms
- Rimonabant, Animals, Anxiety, Behavior, Animal, Cues, Depression, Disease Models, Animal, Dose-Response Relationship, Drug, Male, Mesencephalon, Motivation, Motor Activity, Piperidines, Pyrazoles, Swimming, Time Factors, Tobacco Use Disorder, Signal Transduction, Weight Loss, Behavior, Addictive, Rats, Wistar, Maze Learning, Rats, Long-Evans, Receptor, Cannabinoid, CB1, Drug Inverse Agonism, Drug-Seeking Behavior, Dopaminergic Neurons, Tobacco Use Cessation Devices, Cannabinoid Receptor Antagonists
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