Actions of the beta-carboline ZK 93426 in an animal test of anxiety and the holeboard: interactions with Ro 15-1788.
The effects of the beta-carboline ZK 93426, a putative benzodiazepine receptor antagonist, were investigated in the social interaction test of anxiety and in the holeboard. Like the receptor antagonist Ro 15-1788, ZK 93426 (2.5-10 mg/kg) caused a specific reduction in social interaction (interpreted as an anxiogenic effect) and caused a significant elevation in exploratory head-dipping (5 mg/kg). When low (ineffective) doses of both compounds (1 mg/kg ZK 93426; 4 mg/kg Ro 15-1788) were administered together they significantly reduced social interaction. No further reductions in social interaction were observed when effective doses of both compounds (5 mg/kg ZK 93426; 10 mg/kg Ro 15-1788) were tested in combination; it is likely that this is due to almost total benzodiazepine receptor occupancy at effective doses of either compound. When doses of each compound (5 mg/kg ZK 93426; 10 mg/kg Ro 15-1788) that resulted in stimulation of head-dipping were examined in combination, the elevation in exploration was no longer observed. Since at higher doses of both compounds there is an attenuation of the elevation in head-dipping, it is again likely that the effects of the two compounds are additive.
D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects; D005442:Flumazenil; D007398:Interpersonal Relations; D008297:Male; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects
D001570:Benzodiazepinones; D002243:Carbolines; D011963:Receptors, GABA-A; D005442:Flumazenil; C042568:ZK 93426