Effects of genetic background and null mutation of 5-HT1A receptors on basal and stress-induced body temperature: modulation by serotonergic and GABAA-ergic drugs

Eur J Pharmacol. 2006 Nov 21;550(1-3):84-90. doi: 10.1016/j.ejphar.2006.08.058. Epub 2006 Sep 8.


The stress-induced hyperthermia procedure, in which effects of drugs on basal (T(1)) and stress-induced body temperature (T(2)) are measured, predicts anxiolytic drug effect. Serotonergic drugs alter these responses and here, we studied the role of 5-HT(1A) receptors in stress-induced hyperthermia by using 5-HT(1A) receptor knockout mice. Three strains (129/Sv, Swiss Webster and C57Bl6) were used because genetic background can significantly modulate the null phenotype. We found that GABA-ergic drugs with an anxiolytic profile and stimulate alpha(2) subunit containing GABA(A) receptors, including diazepam and L838,417, result in reduced DeltaT (DeltaT=T(2)-T(1)). The alpha(1) subunit containing GABA(A) receptor was found to be primarily involved in regulation of basal body temperature T(1) and its stimulation can induce hypothermia. In addition, stimulation of 5-HT(1A) receptors by buspirone results in a reduced DeltaT, while stimulation of 5-HT(7) receptors primarily results in hypothermia. The null mutation of 5-HT(1A) receptors resulted in differences in drug-sensitivity that was further modulated by the genetic background. In particular, the null mutation on the SW and C57Bl6 backgrounds resulted in differential diazepam/L838,417 and 5-CT responses respectively. This indicates an interaction between the 5-HT(1A) receptor and genetic background and demonstrates the importance of selecting the background strain in a receptor knockout model.

MeSH terms

  • Animals
  • Body Temperature / drug effects
  • Body Temperature / genetics
  • Body Temperature / physiology*
  • Body Temperature Regulation / drug effects
  • Buspirone / pharmacology
  • Diazepam / pharmacology
  • Fever / physiopathology
  • Flumazenil / pharmacology
  • Fluorobenzenes / pharmacology
  • GABA Agonists / pharmacology
  • GABA Modulators / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pyridines / pharmacology
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / genetics*
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Receptors, GABA-A / drug effects*
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology
  • Serotonin Agents / pharmacology*
  • Serotonin Receptor Agonists / pharmacology
  • Stress, Psychological / physiopathology*
  • Triazoles / pharmacology
  • Zolpidem


  • Fluorobenzenes
  • GABA Agonists
  • GABA Modulators
  • Pyridines
  • Receptors, GABA-A
  • Serotonin Agents
  • Serotonin Receptor Agonists
  • Triazoles
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Flumazenil
  • Zolpidem
  • L 838,417
  • 5-carboxamidotryptamine
  • Diazepam
  • Buspirone