Asymmetrical cross-tolerance between morphine and scopolamine induced antinociception in the primate: differential sites of action.

Two experiments explored the role of the cholinergic system in mediating morphine induced analgesia in the rhesus monkey. Experiment 1 tested for cross-tolerance between two antinociceptive compounds, morphine and scopolamine, using the shock titration technqiue. Tolerance to morphine attentuated the response to scopolamine but tolerance to scopolamine had no effect on morphine induced antinociception. In Experiment 2, the shock threshold was not modified by injections of scopolamine or arecoline into brain sites which had previously been found to be responsive (in terms of antinociception) to morphine injections. These findings are interpreted to imply that morphine and scopolamine do not exert their antinociceptive effects through identical neural substrates, although Experiment 1 does suggest a certain degree of overlap between such substrates.