An atropinized heat-stressed rat model: dose response effects and pharmacokinetics

Atropine and other anticholinergic drugs are widely used in common medications and in the treatment of organophosphate poisoning. Man dissipates heat by the evaporation of sweat. Analogously, rats spread saliva over their bodies for evaporative cooling. Atropine inhibits both sweating and salivation. Therefore, we sought to quantitate the effects of atropine in our rat heatstroke model. While heat-stressing adult male rats of 500 or 250 g at 41.5 degrees C, we measured the effects of i.v. atropine (10-4000 micrograms X kg-1) on the following: heating rate (HR), % wt loss (saliva production), and fecal loss (intestinal motility). HR (degree C X min-1) was the most sensitive index of drug activity with a 200 micrograms X kg-1 dose (equivalent to 2 mg in man for organophosphate poisoning) eliciting an increased HR from 0.022 degrees C (saline) to 0.087 degrees C X min-1 (atropine). Atropine (200 micrograms X kg-1) increased HR even if administered 3 h prior to heat exposure. Large (500 g) rats showed an increase in HR with 25 micrograms X kg-1 of atropine, but 250 g rats required 50 micrograms X kg-1. This model could be used to assess the relative effects of other anticholinergic drugs and as a non-dehydrated heatstroke model.