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

Tommy Pattij*, Lucianne Groenink, Ronald S. Oosting, Jan Van der Gugten, Robert A.A. Maes, Berend Olivier

*Corresponding author for this work

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Previous studies in 5-HT1A 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 (GABAA)-benzodiazepine receptor complex sensitivity in both strains, independent from the anxious phenotype. To further investigate these discrepancies, various GABAA-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 GABAA-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 GABAA-benzodiazepine receptor complex functioning.

Original languageEnglish
Article number60594
Pages (from-to)67-74
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number1
Publication statusPublished - 2002

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