APPARENT INSENSITIVITY OF THE HOTPLATE LATENCY TEST FOR DETECTION OF ANTINOCICEPTION FOLLOWING INTRAPERITONEAL, INTRAVENOUS OR INTRACEREBROVENTRICULAR M6G ADMINISTRATION TO RATS

Although morphine-6-glucuronide (M6G) has been shown to be analgesical ly active, the relative involvement of spinal and supraspinal structur es in mediating M6G's pain-relieving effects following central and sys temic administration to rats is unclear. As the tail flick and hotplat e latency tests are reported to quantify antinociception mediated prim arily by spinal and supraspinal mechanisms respectively, these methods were used to determine the comparative ''apparent'' levels of antinoc iception (expressed as percentage maximum possible effect, % MPE) achi eved after M6G or morphine administration. Following i.v. or i.p. M6G (1.9-5.4 mu mol) dosing or i.p. morphine (10 mu mol) dosing, high leve ls of antinociception (>50% MPE) were achieved using the tail flick te st whereas base-line levels of antinociception were observed 30 sec la ter in the same rats using the hotplate test. By contrast, antinocicep tion evoked by i.v. morphine (10 mu mol) exceeded 50% MPE using both t he hotplate and tail flick tests although the ''apparent'' potency was approximately 2.5 times greater using the tail flick test. After i.c. v. dosing, M6G (0.22-3.3 nmol) was significantly (P < .05) more potent when assessed using the tail flick compared with the hotplate test. T aken together, these data strongly indicate that following central and systemic administration, M6G's antinociceptive effects are mediated p rimarily by spinal structures whereas both spinal and supraspinal mech anisms contribute to systemic morphine's antinociceptive effects.