CHARACTERIZATION OF DELTA(9)-TETRAHYDROCANNABINOL AND ANANDAMIDE ANTINOCICEPTION IN NONARTHRITIC AND ARTHRITIC RATS

Little is known about the effectiveness of hg-tetrahydrocannabinol (TH C) and anandamide in blocking mechanical nociception. Even less is kno wn about their antinociceptive efficacy in chronic inflammatory arthri tis induced by Freund's complete adjuvant. The hypothesis was tested t hat THC and anandamide elicit antinociception in the paw pressure test , and that arthritic rats would exhibit a different response. In nonar thritic rats, THC-and anandamide-induced antinociception lasted 90 min and 15 min, respectively, while antinociception lasted 90 min and 30 min, respectively, in arthritic rats. Area under the curve calculation s revealed no effect of arthritis on THC-and anandamide-induced antino ciception. Another hypothesis was that paw pressure thresholds in arth ritic rats reflect chronic cannabinoid receptor stimulation due to ele vations in free anandamide levels. Yet, the CB1 receptor antagonist SR 141716A failed to alter paw pressure thresholds in either nonarthritic or arthritic rats. Further investigation revealed that SR141716A sign ificantly blocked THC antinociception, with no effect on anandamide. T hus, anandamide's effects did not result from CB1 receptor stimulation , and any potential contribution of endogenous anandamide in arthritis was not revealed. Finally, THC and anandamide appear to release an as yet unknown endogenous opioid, because naloxone significantly blocked their effects. This study indicates that anandamide and THC may act a t different receptor sites to modulate endogenous opioid levels in mec hanical nociception. (C) 1998 Elsevier Science Inc.