title: GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.
abstract: Previous studies in 5-HT(1A) receptor knockout (1AKO) mice on a mixed Swiss Websterx129/Sv (SWx129/Sv) and a pure 129/Sv genetic background suggest a differential gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor complex sensitivity in both strains, independent from the anxious phenotype. To further investigate these discrepancies, various GABA(A)-benzodiazepine receptor ligands were tested in different behavioral paradigms in 1AKO and wild type (WT) mice on a 129/Sv background. 1AKO and WT mice responded comparably to alprazolam, flumazenil, alcohol and pentylenetetrazol as measured in the stress-induced hyperthermia paradigm. In addition, sedative-anesthetic effects of pentobarbital measured via the righting reflex were similar and a selected dose of diazepam exerted similar anxiolytic effects in both genotypes in the elevated plus maze. In conclusion, 1AKO mice on a 129/Sv background have undisturbed GABA(A)-benzodiazepine receptor sensitivity in contrast to those described on a mixed Swiss Websterx129/Sv background. The anxious phenotype of 1AKO mice seems to occur independent of the GABA(A)-benzodiazepine receptor complex functioning.
authors.affiliation: Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA, Utrecht, Netherlands. T.Pattij@pharm.uu.nl
authors.forename: Tommy
authors.initials: T
authors.lastname: Pattij
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Oosting
authors.forename: Jan
authors.initials: J
authors.lastname: van der Gugten
authors.forename: Robert A A
authors.initials: RA
authors.lastname: Maes
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005334:Fever / Q000209:etiology / Q000378:metabolism; D005442:Flumazenil / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010433:Pentylenetetrazole / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000235:genetics*; D044263:Receptors, Serotonin, 5-HT1; D012018:Reflex / Q000187:drug effects; D013045:Species Specificity; D013312:Stress, Physiological / Q000150:complications
chemical_list: D014151:Anti-Anxiety Agents; D018756:GABA Antagonists; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D000431:Ethanol; D005442:Flumazenil; D003975:Diazepam; D010433:Pentylenetetrazole; D010634:Phenobarbital; D000525:Alprazolam