Neuroscience 2001 Abstract
| Presentation Number: | 805.3 |
|---|---|
| Abstract Title: | THE ENDOGENOUS CANNABINOID 2-ARACHIDONOYLGLYCEROL INDUCES VOMITING: BLOCKADE BY MARIJUANA AND IT'S SYNTHETIC ANALOGS. |
| Authors: |
Darmani, N. A.*1
1Dept Pharmacol, Kirksville Coll Osteopathic, Kirksville, MO |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Cannabinoids |
| Session: |
805. Neurotransmitters: cannabinoids Poster |
| Presentation Time: | Wednesday, November 14, 2001 3:00 PM-4:00 PM |
| Location: | Exhibit Hall D-28 |
| Keywords: | delta-9-THC, Vomiting, 2-arachidonoylglycerol, anandamide |
We have recently shown that large doses of the cannabinoid CB1 receptor antagonist/inverse agonist SR 141716A induces emesis which can be reversed by Δ9-THC and synthetic cannabinoids. Furthermore, low nonemetic doses of SR 141716A block the antiemetic effect of Δ9-THC against cisplatin-induced vomiting. These studies implicate a role for endogenous cannabinoids in emetic circuits in the least shrew (Cryptotis parva). We investigated the role of 2-arachidonoylglycerol (2-AG), anandamide and methanandamide in causing emesis. 2-AG (0.25 - 10 mg/kg, i.p.) caused a dose-dependent increase in both vomiting frequency (ED50 = 1.13±1.1 mg/kg) and percent of shrews vomiting (ED50 = 0.48±3.48 mg/kg) in the 30 min observation period. Both anandamide (2.5 - 20 mg/kg) and methanandamide (5-10 mg/kg) failed to produce a dose-dependent emetic effect. The possible antiemetic action of psychoactive [Δ9-THC (1-5 mg/kg), WIN 55, 212-2 (0.25 - 5 mg/kg) and CP55, 940 (0.025 - 0.1 mg/kg)] and a nonpsychoactive cannabinoid (cannabidiol 10 mg/kg) was then investigated. The cited cannabinoids were injected i.p. 10 min prior to 2-AG (10 mg/kg, i.p.). The ID50 order of potency of cannabinoids in reversing the emetic effects (reduction in emesis frequency and % animals vomiting) of 2-AG was CP55, 940 (0.026 - 0.05 mg/kg) > WIN 55, 212 (0.16 - 0.2 mg/kg) > Δ9-THC (1.12 - 1.86 mg/kg). Cannabidiol failed to reverse the emetic action of 2-AG. This study reveals that psychoactive cannabinoids possess antiemetic action and provides first evidence for an emetic role for 2-arachidonoylglycerol in vomiting circuits.
Supported by NIH-NIDA Grant DA0767
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
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