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.
Pu
S F
SF
Neuroscience Research Center, Beijing Medical University, People's Republic of China.
Zhuang
H X
HX
Han
J S
JS
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D020109:Devazepide; D004357:Drug Synergism; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000037:antagonists & inhibitors*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010671:Phenylurea Compounds; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058121:L 365260; D009020:Morphine; D020109:Devazepide; D012844:Sincalide