The normal body temperature lowering effect of aspirin in mice and its circadian rhythm

It is generally believed that the effectiveness of salicylates, such as aspirin (ASP), is restricted to the lowering of the body temperature (BT) previously elevated by pyrogens and that salicylates have no effect on normal BT. We present here evidences which demonstrate that ASP does lower the normal BT of mice kept in a 24 degrees C environment. Male ICR mice, housed under a light-dark cycle (LD 12:12h) at a room temperature of 24 +/- 1 degree C and a humidity of 60 +/- 10% with food and water ad libitum, received intraperitoneal injections of ASP 25, 100 and 200 mg.kg-1. The animals showed a significant decline in their rectal temperature and the BT returned to the values that prevailed before drug administration within 4 h. There was an orderly, progressive dose-dependent decrease in BT. A significant circadian rhythm was demonstrated for ASP-induced hypothermal effect in mice. Although a significant circadian rhythm was also demonstrated for the plasma salicylate concentrations at 1 h after dosing, there seems to be no positive relationship between plasma drug concentrations and the drug response. The results suggest that ASP does affect normal BT regulation in mice and that the circadian rhythm change in ASP-induced hypothermal effect may be mainly due to the rhythms in the sensitivity of mice to the drug.