GABA_A-benzodiazepine receptor complex sensitivity in 5-HT_1A receptor knockout mice on a 129/Sv background

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.