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.