We have recently shown that the
cannabinoid CB(1) 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 (Delta(9)-THC). The present study investigates the
cannabinoid receptor mechanisms by which
Delta(9)-THC produces its
antiemetic effects against
cisplatin (20 mg/kg, i.p.)-induced
emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of
Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals
vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective
antiemetic dose of
Delta(9)-THC for the latter
emesis parameters was 2.5 mg/kg. Although
Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from
vomiting (80% protection). The
cannabinoid CB(1) antagonist (
SR 141716A) and not the CB(2) antagonist (
SR 144528), reversed the
antiemetic effects of
Delta(9)-THC in a dose-dependent fashion.
Delta(9)-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
Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects,
Delta(9)-THC is a more potent
antiemetic agent. Both effects are probably mediated via CB(1) receptors in distinct loci.