title: Diazepam and Ro 15-1788 increase absence epilepsy in WAG/Rij rats chronically exposed to diazepam.
abstract: The mechanisms underlying tolerance to benzodiazepines were investigated by injecting diazepam (5 mg/kg) twice daily for 23 days in WAG/Rij rats (an animal model for non-convulsive absence epilepsy). After this the rats received either the agonist, diazepam, or the antagonist, flumazenil (Ro 15-1788). EEG analyses showed that both compounds increased the amount of absence epilepsy-like phenomena. This suggests that repeated administration of diazepam moves the benzodiazepine receptor spectrum towards the inverse agonist end.
authors.affiliation: Department of Comparative and Physiological Psychology, University of Nijmegen, The Netherlands.
authors.forename: B W
authors.initials: BW
authors.lastname: Peeters
authors.forename: C M
authors.initials: CM
authors.lastname: Van Rijn
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: M N
authors.initials: MN
authors.lastname: Titulaer
authors.forename: J M
authors.initials: JM
authors.lastname: Vossen
authors.forename: A M
authors.initials: AM
authors.lastname: Coenen
mesh_terms: D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D005442:Flumazenil / Q000494:pharmacology*; D006993:Hypnotics and Sedatives; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D006993:Hypnotics and Sedatives; D005442:Flumazenil; D003975:Diazepam