Thermoregulatory aspects of environmental exposure to anticholinesterase agents

Anticholinesterase (antiChE) agents can be highly toxic to birds and mammals and constitute a major proportion of the pesticides used throughout the world. AntiChEs consist of the organophosphates (OP), which irreversibly inhibit the enzyme acetylcholinesterase (AChE), and the carbamates (CB), which reversibly inhibit AChE. AChE inhibition elicits cholinergic stimulation in the central nervous system and in peripheral tissues and organs, which can lead to marked dysfunction of homeostatic systems, including temperature regulation. The control of body temperature uses cholinergic pathways in the integration and central processing of thermal information, as well as in the control of thermoeffector responses. Hence, the cholinergic stimulation elicited from exposure to antiChEs has profound effects on body temperature at rest as well as during exercise. Ambient heat and cold stress can also modulate the animal's sensitivity to antiChE exposure. After exposure to most OPs, rodents and other small species undergo a marked hypothermic response lasting up to 24 hours. On the other hand, humans exposed to OP pesticides rarely become hypothermic but rather experience a fever that may last many days. Recent studies monitoring body temperature in OP-exposed, telemetered rats demonstrated that the initial hypothermic response is followed by a period of hyperthermia lasting several days. That the hyperthermia can be blocked with administration of sodium salicylate suggests that the hyperthermia is a fever. Thus, the antiChE-induced effects on body temperature and other physiological systems cannot be explained solely by the immediate consequences of AChE inhibition and stimulation of cholinergic systems. Research into the mechanisms of action of antiChE toxicity will be improved with a better understanding of their effects on temperature regulation.