TY - JOUR T1 - Apparent Insensitivity of the Hotplate Latency Test for Detection of Antinociception Following Intraperitoneal, Intravenous or Intracerebroventricular M6G Administration to Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1326 LP - 1332 VL - 286 IS - 3 AU - Samantha M. South AU - Maree T. Smith Y1 - 1998/09/01 UR - http://jpet.aspetjournals.org/content/286/3/1326.abstract N2 - Although morphine-6-glucuronide (M6G) has been shown to be analgesically active, the relative involvement of spinal and supraspinal structures in mediating M6G’s pain-relieving effects following central and systemic administration to rats is unclear. As the tail flick and hotplate latency tests are reported to quantify antinociception mediated primarily by spinal and supraspinal mechanisms respectively, these methods were used to determine the comparative “apparent” levels of antinociception (expressed as percentage maximum possible effect, % MPE) achieved after M6G or morphine administration. Following i.v. or i.p. M6G (1.9–5.4 μmol) dosing or i.p. morphine (10 μmol) dosing, high levels of antinociception (>50% MPE) were achieved using the tail flick test whereas base-line levels of antinociception were observed 30 sec later in the same rats using the hotplate test. By contrast, antinociception evoked by i.v. morphine (10 μmol) exceeded 50% MPE using both the 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. Taken together, these data strongly indicate that following central and systemic administration, M6G’s antinociceptive effects are mediated primarily by spinal structures whereas both spinal and supraspinal mechanisms contribute to systemic morphine’s antinociceptive effects. The American Society for Pharmacology and Experimental Therapeutics ER -