DIFFERENTIAL PROFILE OF THE CCKB RECEPTOR ANTAGONIST CI-988 AND DIAZEPAM IN THE 4-PLATE TEST

被引:28
作者
DOOLEY, DJ
KLAMT, I
机构
[1] Department of Neuroscience, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, 48106-1047, MI
关键词
CHOLECYSTOKININ; CHOLECYSTOKININ(B) RECEPTOR ANTAGONIST; CI-988; DIAZEPAM; FLUMAZENIL; ONDANSETRON; 4-PLATE TEST; ANXIETY; MOUSE;
D O I
10.1007/BF02244893
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The cholecystokinin(B) receptor antagonist CI-988 ([R-(R*,R*)]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy) carbonyl]amino]propyl]amino]-1-phenylethyl]amino]-4-oxobutanoic acid compound with 1-deoxy-1-(methylamino)-D-glucitol (1:1)) and the benzodiazepine receptor agonist diazepam were tested for potential anxiolytic effects on punished exploratory behavior in the four-plate test using mice. Diazepam (0.31-5 mg/kg PO) increased the number of shocks taken in a dose-dependent manner, an effect blocked by the benzodiazepine receptor antagonist flumazenil. CI-988 (0.00001-1 mg/kg PO) tended to increase the number of delivered shocks over the chosen dose range; this effect was, however, not dose-related or as large as that produced by diazepam. A limited testing of the 5-hydroxytryptamine(3) receptor antagonist ondansetron (0.1 and 1 mg/kg PO) suggested an effect similar to CI-988. These results indicate that distinct and contrasting dose-response profiles exist for these classical and atypical drugs in an animal model of anxiety based on electric shock.
引用
收藏
页码:452 / 454
页数:3
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