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

Abstract

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)

• Authors: J E Barrett, L S Brady, J A Stanley, R S Mansbach, J M Witkin
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 236 Issue 2 Pg. 313-9 (Feb 1986) ISSN: 0022-3565 [Print] United States
• PMID: 2868115 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Anxiety Agents
• Azabicyclo Compounds
• Benzodiazepinones
• Carbolines
• Piperazines
• Receptors, GABA-A
• zopiclone
• Flumazenil
• Chlordiazepoxide
• beta-carboline-3-carboxylic acid ethyl ester

Topics

• Animals
• Anti-Anxiety Agents (administration & dosage, pharmacology)
• Azabicyclo Compounds
• Behavior, Animal (drug effects)
• Benzodiazepinones (administration & dosage, pharmacology)
• Carbolines (administration & dosage, pharmacology)
• Chlordiazepoxide (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Electroshock
• Female
• Flumazenil
• Food
• Male
• Piperazines (administration & dosage, pharmacology)
• Punishment
• Receptors, GABA-A (drug effects)
• Saimiri