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 Webster×129/Sv (SW×129/Sv) and a pure 129/Sv genetic background suggest a differential γ-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 Webster×129/Sv background. The anxious phenotype of 1AKO mice seems to occur independent of the GABA A–benzodiazepine receptor complex functioning.