Lack of effect of CCK B receptor antagonists in ethological and conditioned animal screens for anxiolytic drugs

Lack of effect of CCK B receptor antagonists in ethological and conditioned animal screens for... 213 121 121 1 1 Gerard R. Dawson Nadia M. J. Rupniak Susan D. Iversen Rachel Curnow Spencer Tye Kelly J. Stanhope Mark D. Tricklebank Merck, Sharp and Dohme Research Laboratories Neuroscience Research Centre Terlings Park, Eastwick Road CM20 2QR Harlow Essex UK Abstract The effects of the CCK B receptor antagonists L-365,260, CI-988 and L-740,093, a new compound with improved bioavailability and CNS penetration, were assessed for anxiolytic-like effects in three rat anxiolytic screens sensitive to benzodiazepines, the elevated plus maze (EPM), conditioned suppression of drinking (CSD) and conditioned emotional response (CER) tests. In the EPM, L-740,093 (0.1–1.0 mg/kg), L-365,260 (0.00001–10.0 mg/kg), and CI-988 (0.01–1.0 mg/kg) did not increase the time spent on the open arms of the maze or the number of entries onto the open arms. In contrast, the benzodiazepine receptor partial agonist, bretazenil (0.3–10.0 mg/kg), significantly increased both the time spent on the open arms and the number of open arm entries. In the CSD and the CER tests, L-740,093 (0.1–1.0 mg/kg) L-365,260 (0.0001–0.1 mg/kg) and CI-988 (0.01–10.0 mg/kg) failed to increase suppression ratios compared to the vehicle-treated control rats, whereas, the benzodiazepine receptor partial agonist FG 8205 (10.0 mg/kg) (CSD) and bretazenil (0.3–3.0 mg/kg) (CER) both significantly increased suppression ratios compared to vehicle-treated control rats. In addition, L-365,260 (1.0–50.0 mg/kg), CI-988 (0.1–10.0 mg/kg) and diazepam (0.1–1.0 mg/kg) were assessed in a squirrel monkey conflict procedure. Although diazepam significantly increased suppressed lever pressing rates, L-365,260 and CI-988 were without effect. The present findings provide little support for the hypothesis that CCK B receptor antagonists have anti-anxiety effects in animals. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Lack of effect of CCK B receptor antagonists in ethological and conditioned animal screens for anxiolytic drugs

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Publisher
Springer Journals
Copyright
Copyright © 1995 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
DOI
10.1007/BF02245597
Publisher site
See Article on Publisher Site

Abstract

213 121 121 1 1 Gerard R. Dawson Nadia M. J. Rupniak Susan D. Iversen Rachel Curnow Spencer Tye Kelly J. Stanhope Mark D. Tricklebank Merck, Sharp and Dohme Research Laboratories Neuroscience Research Centre Terlings Park, Eastwick Road CM20 2QR Harlow Essex UK Abstract The effects of the CCK B receptor antagonists L-365,260, CI-988 and L-740,093, a new compound with improved bioavailability and CNS penetration, were assessed for anxiolytic-like effects in three rat anxiolytic screens sensitive to benzodiazepines, the elevated plus maze (EPM), conditioned suppression of drinking (CSD) and conditioned emotional response (CER) tests. In the EPM, L-740,093 (0.1–1.0 mg/kg), L-365,260 (0.00001–10.0 mg/kg), and CI-988 (0.01–1.0 mg/kg) did not increase the time spent on the open arms of the maze or the number of entries onto the open arms. In contrast, the benzodiazepine receptor partial agonist, bretazenil (0.3–10.0 mg/kg), significantly increased both the time spent on the open arms and the number of open arm entries. In the CSD and the CER tests, L-740,093 (0.1–1.0 mg/kg) L-365,260 (0.0001–0.1 mg/kg) and CI-988 (0.01–10.0 mg/kg) failed to increase suppression ratios compared to the vehicle-treated control rats, whereas, the benzodiazepine receptor partial agonist FG 8205 (10.0 mg/kg) (CSD) and bretazenil (0.3–3.0 mg/kg) (CER) both significantly increased suppression ratios compared to vehicle-treated control rats. In addition, L-365,260 (1.0–50.0 mg/kg), CI-988 (0.1–10.0 mg/kg) and diazepam (0.1–1.0 mg/kg) were assessed in a squirrel monkey conflict procedure. Although diazepam significantly increased suppressed lever pressing rates, L-365,260 and CI-988 were without effect. The present findings provide little support for the hypothesis that CCK B receptor antagonists have anti-anxiety effects in animals.

Journal

PsychopharmacologySpringer Journals

Published: Sep 1, 1995

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