Δ9-Tetrahydrocannabinol suppresses vomiting behavior and Fos expression in both acute and delayed phases of cisplatin-induced emesis in the least shrew
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Cisplatin chemotherapy frequently causes severe vomiting in two temporally separated clusters of bouts dubbed the acute and delayed phases. Cannabinoids can inhibit the acute phase, albeit through a poorly understood mechanism. We examined the substrates of cannabinoid-mediated inhibition of both the emetic phases via immunolabeling for serotonin, Substance P, cannabinoid receptors 1 and 2 (CB(1), CB(2)), and the neuronal activation marker Fos in the least shrew (Cryptotis parva). Shrews were injected with cisplatin (10mg/kg i.p.), and one of vehicle, Delta(9)-THC, or both Delta(9)-THC and the CB(1) receptor antagonist SR141716A (2mg/kg i.p.), and monitored for vomiting. Delta(9)-THC-pretreatment caused concurrent decreases in the number of shrews expressing vomiting and Fos-immunoreactivity (Fos-IR), effects which were blocked by SR141716A-pretreatment. Acute phase vomiting induced Fos-IR in the solitary tract nucleus (NTS), dorsal motor nucleus of the vagus (DMNX), and area postrema (AP), whereas in the delayed phase Fos-IR was not induced in the AP at all, and was induced at lower levels in the other nuclei when compared to the acute phase. CB(1) receptor-IR in the NTS was dense, punctate labeling indicative of presynaptic elements, which surrounded Fos-expressing NTS neurons. CB(2) receptor-IR was not found in neuronal elements, but in vascular-appearing structures. All areas correlated with serotonin- and Substance P-IR. These results support published acute phase data in other species, and are the first describing Fos-IR following delayed phase emesis. The data suggest overlapping but separate mechanisms are invoked for each phase, which are sensitive to antiemetic effects of Delta(9)-THC mediated by CB(1) receptors.
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Cannabinoids have been shown to suppress cisplatin-induced emesis in the least shrew.
“Cannabinoids have been shown to suppress cisplatin-induced emesis in the least shrew.117”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [117]
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- Authors
- Ray, A. P., Griggs, L., & Darmani, N. A.
- Affiliations
- Western University of Health Sciences (US)
- Corresponding author
- Darmani, Nissar A.
- ORCID
- Darmani, Nissar A.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 196
- Issue
- 1
- Pages
- 30-36
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC2613838
- OpenAlex
- W2047463238
- Cited by
- 40
- References
- 41
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA115331)
- Topics
- Health Sciences › Medicine › Surgery › Nausea and vomiting management
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- delta-9-tetrahydrocannabinol, cisplatin-induced emesis, chemotherapy-induced vomiting, Fos expression, CB1 receptor, CB2 receptor, SR141716A, solitary tract nucleus, dorsal motor nucleus of the vagus, area postrema, serotonin, substance P, least shrew
- MeSH terms
- Rimonabant, Animals, Brain Stem, Cisplatin, Drug Therapy, Combination, Female, Immunohistochemistry, Injections, Intraperitoneal, Neurons, Piperidines, Pyrazoles, Serotonin, Shrews, Substance P, Dronabinol, Time Factors, Vomiting, Oncogene Proteins v-fos, Solitary Nucleus, Presynaptic Terminals, Microscopy, Confocal, Analgesics, Non-Narcotic, Area Postrema, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2
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