Anticholinergics: Effects on thermoregulation and performance in rats

Abstract

Atropine (AT) induces a dose-dependent increase in rate of rise of core temperature (heating rate) in sedentary heat-stressed rats, a muscarinic anticholinergic (MA) effect which is quantitatively similar to the increase in heating rate seen in heat-exposed men after equivalent atropine dose. In the heat-stressed rat, scopolamine (S) was found to have 16 x the MA effect of AT and, in the present study, aprophen (AP) and trihexyphenidyl (THP) manifested 0.067 x 0.061 x the MA effect of AT. In rats exercising on a treadmill (11 m/min, 6 degrees incline, 26 degrees C), physostigmine (PH) administration resulted in reduced endurance and increased heating rate, both of which were attenuated following AT administration-hypothesized to be a nicotinic anticholinergic (NA) effect. Optimum doses of anticholinergics to reverse the PH-induced decrements were: AT-200 micrograms/kg, S-8-16 micrograms/kg, AP-3000 micrograms/kg, and THP-800 micrograms/kg. These optimum NA doses for AT, S, and AP were the same as those predicted from their MA potency relative to AT in heat-stressed rats. However, it should be noted that 800 micrograms/kg of THP is only 1/4 of the expected 3200 micrograms/kg dose of THP based on MA equivalence to AT. Relative MA activities and optimum doses in PH-treated exercising rats appear to be due to differential MA and NA activities. Thus, a combination of both sedentary heat-stressed and exercising rat models may be useful in predicting relative cholinergic effects of new drugs with both MA and NA effects in man.