GABAA-benzodiazepine receptor complex sensitivity in 5-HT1A receptor knockout mice on a 129/Sv background

Previous studies in 5-HT1A receptor knockout (IAKO) mice on a mixed Swiss Webster x 129/Sv (SW x 129/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 IAKO and wild type (WT) mice on a 129/Sv background. IAKO 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, IAKO mice on a 129/Sv background have undisturbed GABA(A)-benzodiazepine receptor sensitivity in contrast to those described on a mixed Swiss Webster x 129/Sv background. The anxious phenotype of IAKO mice seems to occur independent of the GABAA-benzodiazepine receptor complex functioning. (C) 2002 Elsevier Science B.V. All rights reserved.