Effect on hypothalamic self-stimulation of the novel beta-carbolines ZK 93 426 (a benzodiazepine receptor antagonist) and ZK 91 296 (a putative partial agonist).
Low doses (300 micrograms/kg-1.0 mg/kg) of the novel beta-carboline, ZK 91 296, a putative agonist at the benzodiazepine receptor, produced a significant increase in the rate of variable-interval self-stimulation responding, similar to that found with typical benzodiazepines. This effect was blocked by simultaneous administration of the specific benzodiazepine-receptor antagonists Ro 15-1788 (2.0 mg/kg), and ZK 93 426 (10 mg/kg). Neither antagonist, ZK 93 426 (100 micrograms/kg-10 mg/kg) or Ro 15-1788 (2.0 mg/kg), had any effect on self-stimulation when given alone. Unlike all benzodiazepine-receptor agonists previously tested, higher doses of ZK 91 296 did not depress self-stimulation response rates, even at a dose-level 100 times greater than the maximally stimulant dose. It is uncertain why ZK 91 296 lacks depressant effects: available evidence does not conclusively favour any single current explanation, but is consistent with it acting as a "partial" agonist.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005442:Flumazenil; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012653:Self Stimulation / Q000187:drug effects*
D001570:Benzodiazepinones; D002243:Carbolines; D011963:Receptors, GABA-A; D005442:Flumazenil; C038933:ZK 91296; C042568:ZK 93426