STRESS-INDUCED HYPERTHERMIA IN SINGLY HOUSED MICE

The stress-induced hyperthermia (SIH) paradigm in group-housed mice al lows screening of putative anxiolytic drugs. The group-housed SIH was adapted to singly housed animals in order to drastically reduce the nu mber of animals used. The affect of various stressors on rectal temper ature was measured in order to find a simple and reliable test procedu re. Repeated, but not single disturbance of animals resulted in a stro ng hyperthermia (Delta T) within 10 min. Similar hyperthermic response s were obtained after immobilization for 1 min or rectal temperature m easurement itself. Neither a 120dB acoustic stimulus, nor repeated 1 m A footshocks led to a temperature change, but 2 mA electric footshocks led to hyperthermia. The final test paradigm chosen involved repeated temperature measurement at a 10 min interval, thus providing both inf ormation on basal temperature and Delta T in each animal within a shor t time frame. Repeated temperature measurements at 10 min intervals re vealed a maximum hyperthermia after approximately 30 min, but up to 70 % of the hyperthermia is already present 10 min after the first measur ement. Repeated use of animals at successive daily or weekly intervals resulted in a gradual increase of both the basal temperature and the temperature 10 min later. At short inter-test intervals (one day) Delt a T also decreased, whereas weekly intervals did not affect the amplit ude of Delta T. Prior injection of the animals resulted in modest hype rthermia, that returned to baseline after 60 min. The anxiolytics diaz epam and 5-HT1A receptor agonist flesinoxan dose-dependently suppresse d SIH. The antidepressant amitriptyline lowered temperature levels but did not affect Delta T. The SM model in singly housed mice appears a fast and reproducible screening test for anxiolytic activity. Compared to the group-housed version, the singly-housed SIH enabled a drastic reduction in the number of animals used. (C) 1997 Elsevier Science Inc .