Thermoregulation in laboratory mammals and humans exposed to anticholinesterase agents

The regulation of body temperature is one of many homeostatic functions affected by exposure to anticholinesterase (antiChE) pesticides, and related compounds. In the study of antiChE neurotoxicity, thermoregulatory variables are often used as sensitive physiological indices. Hence, a review on the thermoregulatory aspects of antiChE agents would be useful to researchers in a variety of fields. A reduction in body temperature is a commonly used indicator of antiChE poisoning in laboratory rodents. On the other hand, humans and some other species often shown an elevation in body temperature when exposed to antiChE agents. Hyperthermia has also been noted in animals treated with either low levels of antiChEs or during recovery from high doses of antiChEs. In this review, the literature dealing with the central and peripheral effects of cholinergic agonists and antagonists is reassessed because the thermoregulatory effects of antiChEs are thought to be linked to the activation of cholinergic pathways. This is followed by a thorough review of the studies reporting thermoregulatory responses in laboratory rodents and humans exposed to low and high doses of a variety of antiChE agents, including the organophosphate- (OP) and carbamate- (CB) based pesticides and related drugs. Attention is given to the possible mechanism of action of OPs on thermoregulation in the laboratory rodent including the involvement of behavioral and autonomic processes. The incidence of antiChE-induced hyperthermia (fever) in humans exposed to antiChEs is also addressed. Other topics of antiChE-induced thermoregulatory dysfunction discussed in this review include the role of exercise, heat, and cold stress, tolerance to antiChE agents, and genetic variability. Overall, the mechanism of antiChE-induced changes in body temperature cannot always be explained solely by the immediate consequences of ChE inhibition.