Physostigmine: dose-response effects on endurance and thermoregulation during exercise

Abstract

We previously reported that the administration of 200 ug/kg of physostigmine (PH) to rats exercising on a treadmill resulted in decrements in both endurance (decreased running time to exhaustion) and thermoregulation. However, it was necessary to determine the dose-response effects of PH administration before PH-treated exercising rats could be used as a model with which to examine the relative anticholinergic potency of drugs. In the present work saline, 50, 100, or 200 ug/kg of physostigmine salicylate (0%, 40%, 50%, and 60% whole blood cholinesterase inhibition) was administered to rats (N = 12/ group) prior to treadmill exercise (26°C, 50% rh, 11 m/min, 6° incline). The saline control group ran for 67 ± 6 min (mean ± SE) with a rate of rise of core temperature of 0.051 ± 0.007°C/min. The run times declined (80%, 64% and 48% of control) as rate of rise of core temperature increased (116%, 180%, and 214% of control) in a dose-dependent manner (50, 100, 200 ug/kg PH). Cholinergic sysmptoms such as salivation, tremors, and defecation were also affected in a dose-dependent manner by PH administration. Since cholinergic symptoms, thermoregulatory effects, and endurance decrements all vary in a dose-dependent manner with physostigmine administration, the exercising rat represents a useful model for examining the relative potency of cholinergic therapies.