Stress-induced hyperthermia in mice: effects of flesinoxan on heart rate and body temperature.
Stress-induced hyperthermia in mice has predictive validity for anxiolytic properties of drugs. In this paradigm, 60 min after drug administration rectal temperature is measured, which causes hyperthermia of 1-1.5 degrees C (DeltaT) in about 10 min. Flesinoxan, a selective 5-HT(1A) receptor agonist with anxiolytic-like properties, causes hypothermia, which complicates interpretation of stress-induced hyperthermia. Therefore, we combined flesinoxan treatment and the stress paradigm with radiotelemetric measurement of body temperature and heart rate, which is also related to anxiety. Subjects were either undisturbed or injected with flesinoxan (0-0.1-0.3-1.0 and 3.0 mg/kg), with or without the stress paradigm. Flesinoxan (1.0 and 3.0 mg/kg) caused a relatively long-lasting hypothermia, but did not lower heart rate. The rectal temperature procedure caused hyperthermia and tachycardia. Flesinoxan reduced the stress-induced hyperthermia and the tachycardia evoked by the stress procedure. Continuous radiotelemetric measurement of heart rate, apart from body temperature, revealed that flesinoxan has anxiolytic-like properties in mice.
Bouwknecht
J A
JA
Department of Psychopharmacology, Faculty of Pharmacy, Utrecht University, Sorbonnelaan 16, 3584 CA, Utrecht, Netherlands. j.a.bouwknecht@pharm.uu.nl
Hijzen
T H
TH
van der Gugten
J
J
Maes
R A
RA
Olivier
B
B
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D005334:Fever / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013312:Stress, Physiological / Q000503:physiopathology*; D013686:Telemetry
D014151:Anti-Anxiety Agents; D010879:Piperazines; D017366:Serotonin Receptor Agonists; C056895:flesinoxan