GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background

Eur J Pharmacol. 2002 Jun 28;447(1):67-74. doi: 10.1016/s0014-2999(02)01893-9.

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.

MeSH terms

  • Alprazolam / pharmacology
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Diazepam / pharmacology
  • Ethanol / pharmacology
  • Fever / etiology
  • Fever / metabolism
  • Flumazenil / pharmacology
  • GABA Antagonists / pharmacology
  • Hypnotics and Sedatives / pharmacology
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Knockout
  • Pentylenetetrazole / pharmacology
  • Phenobarbital / pharmacology
  • Receptors, GABA-A / drug effects*
  • Receptors, Serotonin / genetics*
  • Receptors, Serotonin, 5-HT1
  • Reflex / drug effects
  • Species Specificity
  • Stress, Physiological / complications

Substances

  • Anti-Anxiety Agents
  • GABA Antagonists
  • Hypnotics and Sedatives
  • Receptors, GABA-A
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Ethanol
  • Flumazenil
  • Diazepam
  • Pentylenetetrazole
  • Phenobarbital
  • Alprazolam