title: Relationship of agonist efficacy to changes in GABA sensitivity and anticonvulsant tolerance following chronic benzodiazepine ligand exposure.
abstract: Benzodiazepine ligands of differing efficacy including the agonist, diazepam, the partial agonist, Ro 16-6028 and the antagonist, Ro 15-1788, were administered in vivo to rats continuously for 3 weeks. The magnitude of change in various measures of GABA sensitivity could be correlated directly with increasing agonist efficacy: maximal changes were seen following chronic treatment with diazepam, intermediate changes were seen following the partial agonist Ro 16-6028 and no changes were observed following chronic Ro 15-1788 administration. The magnitude of change could also be correlated with increasing potential for tolerance development to anticonvulsant efficacy following chronic exposure to these benzodiazepine ligands.
authors.affiliation: Yale University School of Medicine, Department of Psychiatry, Abraham Ribicoff Research Facilities and Connecticut Mental Health Center, New Haven, CT.
authors.forename: T D
authors.initials: TD
authors.lastname: Hernandez
authors.forename: C
authors.initials: C
authors.lastname: Heninger
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
authors.forename: D W
authors.initials: DW
authors.lastname: Gallager
mesh_terms: D000818:Animals; D000927:Anticonvulsants; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D001640:Bicuculline / Q000378:metabolism / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004361:Drug Tolerance; D004594:Electrophysiology; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000927:Anticonvulsants; D001570:Benzodiazepinones; D001569:Benzodiazepines; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C054626:bretazenil; D003975:Diazepam; D001640:Bicuculline