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 previ ous studies have shown that both CCK-8 and Ang LT are potent anti-opioid su bstances. Intracerebroventricular (i.c.v.) injection of CCK-8 or Ang II dos e-dependently antagonizes morphine-induced analgesia (MIA). In the present study, we observed the combined effect of CCK-g and Ang II in antagonizing MIA. CCK-8 and Ang II were injected intracerebroventricularly to rats in va rious 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 mu g or 1 ng: 5 mu g produced significantly greater effect in antagonizing MI A. The ED50 Of the two ratios are only 18.5% and 27.5%, respectively, of th e theoretical dose of simple addition. We conclude that CCK-8 and Ang II us ed in such dose ratios may antagonize MIA synergistically. (C) 2000 Interna tional Association for the Study of Pain. Published by Elsevier Science B.V . All rights reserved.