Antinociceptive action of cholecystokinin octapeptide (CCK 8) and related peptides in rats and mice: effects of naloxone and peptidase inhibitors.

Cholecystokinin octapeptide (CCK 8) produced significant antinociception in the tail immersion test in the rat, paw pressure test in the rat and acetylcholine-induced writhing test in the mouse after subcutaneous (s.c.) administration. In the hot plate test, CCK 8 (s.c.) showed antinociceptive activity if the latency to lick was used as the end point but if the latency to jump was recorded the antinociceptive effects were not evident. Cholecystokinin tetrapeptide (CCK 4) was shown to be antinociceptive in the writhing but not in the hot plate test after subcutaneous administration and appeared to be less potent than CCK 8 when tested under the same conditions. Antinociception induced by CCK 8 in the hot plate test (lick) could also be demonstrated after direct intracerebroventricular (i.c.v.) injection and this observation was also made with the CCK-related peptide FMRF amide. Antinociception induced by CCK 8 (which did not appear to be associated with reduced locomotor activity) was evident 5 min after intraventricular injection and was maximal at 10 min, the effect lasting over a 30-45 min period. The antinociceptive effect of CCK 8 was antagonised by naloxone and was potentiated by simultaneous administration of the peptidase inhibitors bestatin, thiorphan and captopril.