Neuroscience 2000 Abstract
| Presentation Number: | 812.4 |
|---|---|
| Abstract Title: | Δ<SUP>9</SUP>-Tetrahydrocannabinol prevents chemotherapy-induced vomiting via the activation of cannabinoid CB<SUB>1</SUB> receptors. |
| Authors: |
Darmani, N. A.*1
1Dept Pharmacol, Kirksville Coll Osteopathic Med., Kirksville, MO |
| Primary Theme and Topics |
D. Neurotransmitters, Modulators, Transporters, and Receptors - 54. Cannabinoids |
| Secondary Theme and Topics | J. Disorders of the Nervous System and Aging<br />- 146. Drugs of abuse: opioids and others |
| Session: |
812. Cannabinoids: analgesia Poster |
| Presentation Time: | Thursday, November 9, 2000 11:00 AM-12:00 PM |
| Location: | Hall G-J |
| Keywords: | Delta-9-THC, CB1 Receptor, Vomiting, SR 141716A |
Numerous clinical trials have shown that Δ 9-THC and its synthetic analogs (nabilone and levonantradol) are useful antiemetics in patients receiving chemotherapy. However, the receptor mechanism(s) by which cannabinoids prevent chemotherapy-induced emesis remains unknown. Recently, we have shown that the selective CB1 receptor antagonist SR 141716A can produce emesis in the least shrew in a dose-dependent manner when administered either intraperitoneally (ED50 = 5.5 ± 1.2 mg/kg) or subcutaneously (ED50 = 20.2 ± 1, mg/kg). The latter effect was blocked by Δ9-THC. The purpose of the present study was to investigate: 1) if Δ9-THC can prevent cisplatin-induced emesis in the least shrew, and ii) whether the latter antiemetic effect can be prevented by nonemetic doses of SR 141716A. At 0 time, different groups of shrews received varying doses of Δ9-THC (0, 1, 2.5, 5 and 10 mg/kg, i.p.) and an emetic dose of cisplatin (20 mg/kg, i.p.). The frequency of emesis was recorded for the next 60 min. Administration of Δ9-THC dose-dependently reduced the number of shrews vomiting (ID50 = 1.8 ± 1.6 mg/kg) in response to cisplatin. Administration of the CB1 antagonist SR 141716A or the CB2 antagonist SR 144528 had no effect on cisplatin-induced emesis. However, 10 min prior treatment with nonemetic doses of SR 141716A (0, 1, 5 or 10 mg/kg, s.c.), blocked the ability of Δ9-THC (5 mg/kg, i.p.) to prevent emesis caused by cisplatin. On the other hand, SR 144528 failed to prevent the antiemetic effect of Δ9-THC. These data strongly support the notion that Δ9-THC prevents chemotherapy-induced vomiting via the activation of cannabinoid CB1 receptor.
Supported by NIH Grant DA 12605
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2000 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2000. Online.
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