CHOLECYSTOKININ-OCTAPEPTIDE (CCK-8) ANTAGONIZES MORPHINE ANALGESIA INNUCLEUS-ACCUMBENS OF THE RAT VIA THE CCK-B RECEPTOR

The analgesic effect of systemic morphine (4 mg/kg, s.c.) was antagoni zed 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 rec eptor antagonist, at 50 ng and 200 ng and by L-365,260, a CCK-B recept or antagonist, at 5 ng administered bilaterally to the nucleus accumbe ns. A marked potentiation of morphine analgesia was achieved by intra- nucleus accumbens injection of 200 ng devazepide or 5 ng L-365,260. Si nce 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.