Cited by 84Cannabis and Cannabinoid ResearchNeuroendocrine regulation and behaviorNeuropeptides and Animal Physiology

Prevention of Cannabinoid Withdrawal Syndrome by Lithium: Involvement of Oxytocinergic Neuronal Activation

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Cui, Shu-Sen, Bowen, Rudy C., Gu, Gui-Bao, Hannesson, Darren K., Yu, Peter H., Zhang, Xia·2001·The Journal of Neuroscience

Abstract

Cannabis (i.e., marijuana and cannabinoids) is the most commonly used illicit drug in developed countries, and the lifetime prevalence of marijuana dependence is the highest of all illicit drugs in the United States. To provide clues for finding effective pharmacological treatment for cannabis-dependent patients, we examined the effects and possible mechanism of lithium administration on the cannabinoid withdrawal syndrome in rats. A systemic injection of the mood stabilizer lithium, at serum levels that were clinically relevant, prevented the cannabinoid withdrawal syndrome. The effects of lithium were accompanied by expression of the cellular activation marker Fos proteins within most oxytocin-immunoreactive neurons and a significant increase in oxytocin mRNA expression in the hypothalamic paraventricular and supraoptic nuclei. Lithium also produced a significant elevation of oxytocin levels in the peripheral blood. We suggest that the effects of lithium against the cannabinoid withdrawal syndrome are mediated by oxytocinergic neuronal activation and subsequent release and action of oxytocin within the CNS. In support of our hypothesis, we found that the effects of lithium against the cannabinoid withdrawal syndrome were antagonized by systemic preapplication of an oxytocin antagonist and mimicked by systemic or intracerebroventricular injection of oxytocin. These results demonstrate that oxytocinergic neuronal activation plays a critical role in the action of lithium against the cannabinoid withdrawal syndrome in rats, thus providing a potentially novel strategy for the treatment of cannabis dependence in humans.

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Crossref · 10.1523/jneurosci.21-24-09867.2001

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  1. Gelder M, Mayou R, Geddes J (1999) In: Psychiatry, Ed 2 (Gelder M, Mayou R, Geddes J, eds), pp 353-354. New York: Oxford UP.
  2. Sofroniew MV (1985) Vasopressin, oxytocin and their related neuro- physins. In: Handbook of chemical neuroanatomy, Vol 4, GABA and neuropeptides in the CNS, Part I (Bjorklund A, Hokfelt T, eds), pp 93-165. Amsterdam: Elsevier.

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Authors
Cui, S.-S., Bowen, R. C., Gu, G.-B., Hannesson, D. K., Yu, P. H., & Zhang, X.
Affiliations
University of Saskatchewan (CA)
Venue
The Journal of Neuroscience
Published
2001-12-15
Volume
21
Issue
24
Pages
9867-9876
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2147042597
Cited by
84
References
57
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 3 · 2013: 4 · 2012: 7
FWCI
0.89
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
lithium, oxytocin, cannabis use disorder, oxytocinergic neurons, Fos expression, hypothalamic paraventricular nucleus, supraoptic nucleus, oxytocin antagonist, pharmacological treatment of addiction
MeSH terms
Animals, Behavior, Animal, Camphanes, Brain, Cannabinoids, Densitometry, Dose-Response Relationship, Drug, Immunohistochemistry, Lithium, Male, Morpholines, Neurons, Oxytocin, Piperazines, Pyrazoles, Radioimmunoassay, Receptors, Drug, Substance Withdrawal Syndrome, Dronabinol, Proto-Oncogene Proteins c-fos, In Situ Hybridization, Receptors, Oxytocin, Rats, Long-Evans, Receptors, Cannabinoid, Rats

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