Behavioral studies with anxiolytic drugs. II. Interactions of zopiclone with ethyl-beta-carboline-3-carboxylate and Ro 15-1788 in squirrel monkeys

JE Barrett, LS Brady, JA Stanley, RS Mansbach and JM Witkin

The effects of zopiclone (0.1-100 mg/kg) were studied alone and in combination with the benzodiazepine receptor antagonist Ro 15-1788 and the inverse agonist ethyl-beta-carboline-3-carboxylate (beta-CCE). Under one procedure, food-maintained responding of squirrel monkeys was punished during one component of a multiple schedule. Each 30th response during both components produced food and, during the punishment component, also produced electric shock. Intermediate doses of zopiclone (0.3-30 mg/kg) did not affect or decreased unpunished responding and produced large increases in punished responding; higher zopiclone doses decreased responding under both conditions. beta-CCE (0.1-3 mg/kg) reversed both the rate-increasing and the rate-decreasing effects of zopiclone under each condition, producing a dose-dependent shift to the right of the zopiclone dose-effect curves. All doses of beta-CCE higher than 0.1 mg/kg decreased responding when given alone. Ro 15-1788 (0.1 or 1 mg/kg), which had no effect on punished or unpunished responding, reversed both the rate-increasing and the rate- decreasing effects of zopiclone. Under a second procedure, zopiclone increased responding of squirrel monkeys maintained by food under a 5- min fixed-interval schedule at doses that did not affect or decreased responding comparably maintained in an alternate component by response- produced electric shock. These effects were also reversed by both Ro 15- 1788 and beta-CCE. When administered alone, beta-CCE produced effects opposite those of zopiclone and the benzodiazepines by decreasing responding maintained by food and increasing shock-maintained responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 236, Issue 2, pp. 313-319, 02/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics

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