Behavioral studies with anxiolytic drugs. II. Interactions of zopiclone with ethyl-beta-carboline-3-carboxylate and Ro 15-1788 in squirrel monkeys.
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)
Barrett
J E
JE
Brady
L S
LS
Stanley
J A
JA
Mansbach
R S
RS
Witkin
J M
JM
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D053961:Azabicyclo Compounds; D001522:Behavior, Animal / Q000187:drug effects; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D002243:Carbolines / Q000008:administration & dosage / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock; D005260:Female; D005442:Flumazenil; D005502:Food; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011678:Punishment; D011963:Receptors, GABA-A / Q000187:drug effects; D012453:Saimiri
D014151:Anti-Anxiety Agents; D053961:Azabicyclo Compounds; D001570:Benzodiazepinones; D002243:Carbolines; D010879:Piperazines; D011963:Receptors, GABA-A; C515050:zopiclone; D005442:Flumazenil; D002707:Chlordiazepoxide; C024915:beta-carboline-3-carboxylic acid ethyl ester