Effects of genetic background and null mutation of 5-HT sub(1A) receptors on basal and stress-induced body temperature: Modulation by serotonergic and GABA sub(A)-ergic drugs

• Published in: European journal of pharmacology 2006-11, Vol.550 (1-3), p.84-90
• Main Authors: Van Bogaert, Meg, Oosting, Ronald, Toth, Miklos, Groenink, Lucianne, Van Oorschot, Ruud, Olivier, Berend
• Format: Article
• Language: English
• ISSN: 0014-2999
• DOI: 10.1016/j.ejphar.2006.08.058

The stress-induced hyperthermia procedure, in which effects of drugs on basal (T sub(1)) and stress-induced body temperature (T sub(2)) are measured, predicts anxiolytic drug effect. Serotonergic drugs alter these responses and here, we studied the role of 5-HT sub(1A) receptors in stress- induced hyperthermia by using 5-HT sub(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 a sub(2) subunit containing GABA sub(A) receptors, including diazepam and L838,417, result in reduced T (T = T sub(2) - T sub(1)). The a sub(1) subunit containing GABA sub(A) receptor was found to be primarily involved in regulation of basal body temperature T sub(1) and its stimulation can induce hypothermia. In addition, stimulation of 5-HT sub(1A) receptors by buspirone results in a reduced T, while stimulation of 5-HT sub(7) receptors primarily results in hypothermia. The null mutation of 5-HT sub(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 sub(1A) receptor and genetic background and demonstrates the importance of selecting the background strain in a receptor knockout model.