Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB1 receptors in the least shrew

Document Type

Article

Publication Title

Pharmacology Biochemistry and Behavior

Abstract

We have recently shown that the cannabinoid CB1 receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Δ9-THC). The present study investigates the cannabinoid receptor mechanisms by which Δ9-THC produces its antiemetic effects against cisplatin (20 mg/kg, ip)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Δ9-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID50 = 1.8 ± 1.6 mg/kg) and the frequency of vomits (ID50 = 0.36 ± 1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Δ9-THC for the latter emesis parameters was 2.5 mg/kg. Although Δ9-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB1 antagonist (SR 141716A) and not the CB2 antagonist (SR 144528), reversed the antiemetic effects of Δ9-THC in a dose-dependent fashion. Δ9-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Δ9-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Δ9-THC is a more potent antiemetic agent. Both effects are probably mediated via CB1 receptors in distinct loci. © 2001 Elsevier Science Inc.

First Page

239

Last Page

249

DOI

10.1016/S0091-3057(01)00531-7

Publication Date

7-4-2001

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