ANTINOCICEPTIVE ACTIONS OF CANNABINOIDS FOLLOWING INTRAVENTRICULAR ADMINISTRATION IN RATS

Intraventricular administration of 5 or 20 mu g of the cannabinoids WI N55,212-2 and CP-55,940 markedly reduced rat's responses to noxious th ermal stimuli in the tail-flick test; no significant effect was found at 1 mu g. The dose-response curves were steep and monotonic, the onse t was rapid, and the effect lasted about an hour at the highest dose. In contrast to their antinociceptive actions, WIN55,212-2 and CP-55,94 0 failed to alter the latency of righting reflexes at the highest dose , suggesting that motor impairment did not cause the decreased respons iveness to the thermal stimulus. Finally, an assessment of the biodist ribution of intraventricularly administered [H-3]WIN55,212-2 in brain and spinal cord at the time of maximal antinociception revealed that t he drug was confined to the brain. The levels of [H-3]WIN55,212-2 foun d in S-3-S-4, the location of the spinal mechanisms for tail-flick, we re below the limit of detectability. Together, these findings provide direct evidence that the antinociceptive effects of cannabinoids are m ediated, at least in part, by their actions in the brain.