title: Chronic treatment with Ro 15-1788 distinguishes between its benzodiazepine antagonist, agonist and inverse agonist properties.
abstract: Ro 15-1788 (flumazepil) is an imidazodiazepine that is able to antagonise most of the behavioural actions of the benzodiazepines, as well as having some intrinsic effects. Acute administration of Ro 15-1788 (10 mg/kg) decreases social interaction between male rats and elevates exploratory head-dipping. After 5 days of pretreatment there was tolerance to the former effect, although Ro 15-1788 retained its ability to antagonise the effects on social interaction of the beta-carboline, FG 7142. Ro 15-1788 also retained its ability to elevate head-dipping: additionally, the chronically-treated rats had elevated motor activity and rearing scores. The acute effects of lorazepam in the holeboard were unchanged by chronic pretreatment with Ro-15-1788. The plasma and brain concentrations after acute administration of lorazepam were unchanged following chronic administration of Ro 15-1788. After chronic treatment the brain concentrations of Ro 15-1788 were unchanged. It is unlikely that pharmacokinetic factors could underlie the different behavioural changes following chronic treatment.
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D001923:Brain Chemistry; D002243:Carbolines / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D004361:Drug Tolerance; D005106:Exploratory Behavior / Q000187:drug effects; D005442:Flumazenil; D008140:Lorazepam / Q000008:administration & dosage; D008297:Male; D051381:Rats; D012919:Social Behavior
chemical_list: D001570:Benzodiazepinones; D002243:Carbolines; D005442:Flumazenil; C035874:FG 7142; D008140:Lorazepam