The CCK-B receptor antagonist Cl 988 reverses tolerance to morphine in rats

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Abstract
THE ability of the selective cholecystokinin-B (CCK-B) receptor antagonist CI 988 to reverse tolerance to morphine's antinociceptive effect was investigated with the hot-plate test in Sprague-Dawley rats. Tolerance was induced by subcutaneous (s.c.) injection of 10 mg kg−1 morphine twice daily for four days. On the fifth day rats were administered CI 988 (10 mg kg−1) or saline plus 5 mg kg−1 morphine s.c. Significant antinociception was observed in the group that received the CCK-B antagonist plus morphine, whereas the saline plus morphine group exhibited total tolerance. These results suggest that upregulation of the endogenous CCK system during repeated morphine administration may have an important role in the development of opiate tolerance.

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