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

• Published in: European journal of pharmacology Vol. 550; no. 1-3; pp. 84 - 90
• Main Authors: VAN BOGAERT, Meg, OOSTING, Ronald, TOTH, Miklos, GROENINK, Lucianne, VAN OORSCHOT, Ruud, OLIVIER, Berend
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 21-11-2006
• Subjects: Animals; Biological and medical sciences; 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; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Pharmacology. Drug treatments; 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; Drug; Genetic background; Strain differences; Body temperature; Rodentia; Knockout,Body temperature; Stress-induced hyperthermia; 5-HT7 serotonin receptor; Strain specificity; Stress; 5-HT7 receptor; Vertebrata; Mammalia; 5-HT1A Serotonine receptor; Gene; Mouse; Animal; Genetics; Mutation; GABAA receptor; Gabaergic receptor A; Induced hyperthermia; 5-HT1A receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.08.058

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.