Synergistic effect of cholecystokinin octapeptide and angiotensin II in reversal of morphine induced analgesia in rats.

The aim of this paper is to study the synergistic anti-analgesic effect of angiotensin II (Ang II) plus cholecystokinin octapeptide (CCK-8). Our previous studies have shown that both CCK-8 and Ang II are potent anti-opioid substances. Intracerebroventricular (i.c.v.) injection of CCK-8 or Ang II dose-dependently antagonizes morphine-induced analgesia (MIA). In the present study, we observed the combined effect of CCK-8 and Ang II in antagonizing MIA. CCK-8 and Ang II were injected intracerebroventricularly to rats in various proportions and doses. The results were analyzed with isobolographic analysis. Combined injection of CCK-8 and Ang II in a ratio of 1 ng: 2.5 microg or 1 ng: 5 microg produced significantly greater effect in antagonizing MIA. The ED(50) of the two ratios are only 18.5% and 27.5%, respectively, of the theoretical dose of simple addition. We conclude that CCK-8 and Ang II used in such dose ratios may antagonize MIA synergistically.