Abstract
The cholecystokininB receptor antagonist CI-988 ([R-(R*,R*)]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[(tricyclo[3.3.1. 13,7]dec-2-yloxy)carbonyl]amino]-propyl]amino]-1-phenylethyl]amino]-4-oxobbutanoic 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-hydroxytryptamine3 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aron C, Simon P, Larousse C, Boissier JR (1971) Evaluation of a rapid technique for detecting minor tranquilizers. Neuropharmacology 10:459–469
Dunn RW, Carlezon WA Jr, Corbett R (1991) Preclinical anxiolytic versus antipsychotic profiles of the 5-HT3 antagonists ondansetron, zacopride, 3α-tropanyl-1H-indole-3-carboxylic acid ester and 1αH,3α,5αH-tropan-3-yl-3,5-dichlorobenzoate. Drug Dev Res 23:289–300
File SE, Johnston AL (1989) Lack of effects of 5HT3 receptor antagonists in the social interaction and elevated plus-maze tests of anxiety in the rat. Psychopharmacology 99:248–251
Hughes J, Boden P, Costall B, Domeney A, Kelly E, Horwell DC, Hunter JC, Pinnock RD, Woodruff GN (1990) Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci USA 87:6728–6732
Jones BJ, Costall B, Domeney AM, Kelly ME, Naylor RJ, Oakley NR, Tyers MB (1988) The potential anxiolytic activity of GR38032F, a 5-HT3 receptor antagonist. Br J Pharmacol 93:985–93
Powell KR, Barrett JE (1991) Evaluation of the effects of PD-134308 (CI-988), a CCK-B antagonist, on the punished responding of squirrel monkeys. Neuropeptides [Suppl.] 19:75–78
Rataud J, Darche F, Piot O, Stutzmann J-M, Boehme GA, Blanchard J-C (1991) Anxiolytic effect of CCK-antagonists on plusmaze behavior in mice. Brain Res 548:315–317
Singh L, Field MJ, Hughes J, Menzies R, Oles RJ, Vass CA, Woodruff GN (1991a) The behavioural properties of CI-988, a selective cholecystokininB receptor antagonist. Br J Pharmacol 104:239–245
Singh L, Lewis AS, Field MJ, Hughes J, Woodruff GN (1991b) Evidence for an involvement of the brain cholecystokinin B receptor in anxiety. Proc Natl Acad Sci USA 88:1130–1133
Tallarida RJ, Murray RB (1987) Manual of pharmacologic calculations with computer programs, 2nd edn. Springer, New York
Woodruff GN, Hill DR, Boden P, Pinnock R, Singh L, Hughes J (1991) Functional role of brain CCK receptors. Neuropeptides [Suppl.] 19:45–56
Wright IK, Heaton M, Upton N, Marsden CA (1992) Comparison of acute and chronic treatment of various serotonergic agents with those of diazepam and idazoxan in the rat elevated X-maze. Psychopharmacology 107:405–414
Young R, Johnson DN (1991) A fully automated light/dark apparatus useful for comparing anxiolytic agents. Pharmacol Biochem Behav 40:739–743
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dooley, D.J., Klamt, I. Differential profile of the CCKB receptor antagonist CI-988 and diazepam in the four-plate test. Psychopharmacology 112, 452–454 (1993). https://doi.org/10.1007/BF02244893
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244893