Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in nucleus accumbens of the rat via the CCK-B receptor.

The analgesic effect of systemic morphine (4 mg/kg, s.c.) was antagonized in a dose-dependent manner by cholecystokinin octapeptide (CCK-8) (0.1-0.5 ng) administered bilaterally to the nucleus accumbens of the rat. This effect of CCK-8 could be reversed by devazepide, a CCK-A receptor antagonist, at 50 ng and 200 ng and by L-365,260, a CCK-B receptor antagonist, at 5 ng administered bilaterally to the nucleus accumbens. A marked potentiation of morphine analgesia was achieved by intra-nucleus accumbens injection of 200 ng devazepide or 5 ng L-365,260. Since the effect of L-365,260 in antagonizing the anti-opioid effect of CCK-8 in the nucleus accumbens is 40 times more potent than devazepide, it is suggested that the anti-opioid effect of CCK-8 is mediated by CCK-B receptors. In conclusion, nucleus accumbens is a strategic site where CCK-8 exerts an anti-opioid activity, most probably via the CCK-B receptors.