Antagonism of the anticonflict effects of chlordiazepoxide by beta-carboline carboxylic acid ethyl ester, Ro 15-1788 and ACTH(4--10).
The antagonism of the anticonflict effect of chlordiazepoxide (CDP) by beta-carboline carboxylic acid ethyl ester (BCCE), Ro 15-1788 and ACTH(4--10) has been evaluated in the Geller-Seifter rat conflict test in which CDP increases punished (conflict), but not unpunished responding. BCCE (0.5--10 micrograms ICV) produced a dose-dependent reduction in the anticonflict activity of CDP. This was also significantly reduced by Ro 15-1788 (25 mg/kg IP) and a high dose of ACTH(4--10) (5 micrograms ICV). None of these test compounds had a marked direct effect on punished or unpunished responding in the dose used. These experiments provide further physiological support for the suggestion from binding studies that BCCE and Ro 15-1788 act on benzodiazepine receptors. However, the ability of ACTH(4--10) to reduce the anticonflict effect of CDP may be by some other, possibly opioid, mechanism.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003220:Conflict, Psychological; D005239:Fear / Q000187:drug effects; D005442:Flumazenil; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009115:Muridae; D010446:Peptide Fragments / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D012055:Reinforcement Schedule
D001570:Benzodiazepinones; D002243:Carbolines; D007211:Indoles; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005442:Flumazenil; D002707:Chlordiazepoxide; C024915:beta-carboline-3-carboxylic acid ethyl ester; D000324:Adrenocorticotropic Hormone; C011394:ACTH (4-10)