The effects of Ro 15-4513 on the behavioral actions of ethanol in an operant reaction time task and a conflict test.
Ro 15-4513, an analogue of the benzodiazepine receptor antagonist Ro 15-1788, has been reported to selectively block the anxiolytic and intoxicating properties of ethanol in rats. To examine the specificity and selectivity of this ethanol antagonism, the effects of Ro 15-4513 were tested on the actions of ethanol in an operant reaction time and conflict test in rats. The operant reaction time task involved holding down a lever for 0.25-2.0 seconds to obtain food, and animals treated with 1 g/kg of ethanol showed a significant disruption in performance. This disruptive effect was reversed by Ro 15-4513 in doses of 1.5-5.0 mg/kg. Ro 15-4513 was also tested in an operant conflict paradigm sensitive to alcohol effects. Ro 15-4513 (0, 1.5, 3.0, 6.0 mg/kg) produced a significant decrease in both punished and unpunished responding in the conflict test. Ethanol (0.75 g/kg), pentobarbital (5 mg/kg) and chlordiazepoxide (5 mg/kg) all produced a significant release of punished responding that was blocked by pretreatment with 6.0 mg/kg Ro 15-4513, but again Ro 15-4513 suppressed responding on its own at this dose. These results suggest that Ro 15-4513 has inverse agonist properties that may explain its ethanol-antagonist action.
Koob
G F
GF
Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Percy
L
L
Britton
K T
KT
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time
D001386:Azides; D001569:Benzodiazepines; D000431:Ethanol; D002707:Chlordiazepoxide; C042957:Ro 15-4513; D010424:Pentobarbital