Stress-induced hyperthermia in the 5-HT1A receptor knockout mouse is normal

Background: Several studies on serotonin 1A (5-HT1A) receptor knockout mice in different genetic backgrounds indicate that such mice display a more an xious phenotype than their corresponding wild types. We hypothesized that t he 5-HT1A receptor knockout mice would show a different phenotype than the wild type mice in the stress-induced hyperthermia (SIH) paradigm, which tes ts putative anxiolytic effects of drugs. Moreover, on pharmacologic challen ges with the 5-HT1A receptor agonist flesinoxan we expected an absence of t he functional response in knockout mice relative to wild type mice. Methods: Effects of the 5-HT1A receptor agonist flesinoxan, alone or in com bination with the 5-HT1A receptor antagonist WAY-100635, and the gamma -ami nobutyric acid A (GABA(A))-benzodiazepine receptor agonist diazepam were st udied in the SIH paradigm in male 129/Sv 5-HT1A receptor knockout and wild type mice. In addition, the effects of flesinoxam on plasma corticosterone concentrations were determined. Results: Plasma corticosterone concentrations were dose dependently elevate d by flesinoxan in wild type mice but not in knockout mice. Flesinoxan dose dependently decreased SIH in wild type mice but not in knockout mice. The flesinoxan effect in wild type mice was blocked by WAY-100635. Furthermore, diazepam decreased SIH in both genotypes. There were no differences in bas ic SIH responses between wild type and knockout mice. Conclusions: 5-HT1A receptor knockout mice display a normal SIH response, a nd results indicate, based on the SIH, that the GABA(A)-benzodiazepine rece ptor complex functions normally. Biol Psychiatry 2001;49:569-574 (C) 2001 S ociety of Biological Psychiatry.