ANALGESIC, RESPIRATORY AND HEART-RATE EFFECTS OF CANNABINOID AND OPIOID AGONISTS IN RHESUS-MONKEYS - ANTAGONIST EFFECTS OF SR 141716A

This study characterized the antinociceptive, respiratory and heart ra te effects of the cannabinoid receptor agonists Delta-9-tetrahydrocann abinol (Delta-9-THC) and WIN 55212 nyl)methyl]pyrol-[1,2,3-de]-1,4-ben zoxazin-6-yl)(1 -naphtalenyl)methanone monomethanesulfonate}, N-arachi donyl ethanolamide (anandamide) and the mu and kappa opioid receptor a gonists heroin and U69593, alone and in conjunction with a cannabinoid receptor antagonist, SR 141716A ichlorophenyl)-4-methyl-1H-pyrazole-- 3-carboxamide hydrochioride] and an opioid receptor antagonist, quadaz ocine, in rhesus monkeys (Macaca mulatta). Using 12 adult rhesus monke ys, latencies to remove the tail from a 50 degrees C water bath, respi ration in 5% CO2 and heart rate were measured. When administered alone , SR 141716A (1.8, 5.6 mg/kg i.m.) did not alter nociception, respirat ion or heart rate. Delta-9-THC (0.1-10 mg/kg i.m.) and WIN 55212 (0.1- 10 mg/kg i.m.) dose-dependently increased antinociception and dose-dep endently decreased respiratory minute and tidal volumes and heart rate . These antinociceptive, respiratory and heart rate effects were rever sed by SR 141716A but not by the opioid antagonist quadazocine (1 mg/k g i.m.). Anandamide (10 mg/kg i.m.) also produced antinociception. Her oin (0.01-10 mg/kg i.m.) and U69593 (0.013.2 mg/kg i.m.) also dose-dep endently increased antinociception and decreased respiratory and heart rate measures; these effects were antagonized by quadazocine but not by SR 141716A. These results demonstrate selective and reversible anta gonism of cannabinoid behavioral effects by SR 141716A in rhesus monke ys.