The effect of agonists at the GABA-benzodiazepine-receptor-complex on the proconflict effect induced by beta-CCM and pentetrazol in rats.
The effect of anxiolytics, benzodiazepine (BZP), diazepam (DZP), non-BZP zopiclone (ZOP) and phenobarbital (PBT), on the proconflict effect induced by methyl-beta-carboline-3-carboxylate (beta-CCM) or by pentetrazol (PTZ) was investigated. The proconflict effect of beta-CCM and PTZ was reduced by these anxiolytics and aminooxyacetic acid (AOAA). In addition, isoniazid produced proconflict activity. Therefore, it is suggested that anxiolytics facilitate the GABA-ergic function, causing the inhibition of the proconflict effect. Although both propyl-beta-carboline-3-carboxylate (beta-CCP) and Ro15-1788 did not produce proconflict activity, they reduced the proconflict effect induced by beta-CCM but not by PTZ. These data clearly show that beta-CCM exerts the proconflict effect through interaction with BZP receptor and that there are behavioral similarities between beta-CCP and Ro15-1788. In this study, we additionally observed the time latency until the rat began to drink the water. beta-CCM and PTZ prolonged this latency in a dose-dependent manner. However, AOAA could not reduce the prolonged latency induced by beta-CCM and by PTZ, and anxiolytics and beta-CCP could not reduce the prolonged latency induced by beta-CCM. The mechanism of the prolongation of latency induced by beta-CCM and PTZ seems to be different from that of the proconflict effect.
Nagatani
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yamamoto
T
T
Sugihara
T
T
Ueki
S
S
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D053961:Azabicyclo Compounds; D002243:Carbolines / Q000494:pharmacology*; D003220:Conflict, Psychological; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D006993:Hypnotics and Sedatives; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D053961:Azabicyclo Compounds; D002243:Carbolines; D003292:Convulsants; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011963:Receptors, GABA-A; C515050:zopiclone; D000625:Aminooxyacetic Acid; D005442:Flumazenil; C036150:beta-carboline-3-carboxylic acid methyl ester; D003975:Diazepam; D010433:Pentylenetetrazole; D010634:Phenobarbital