Effects of Toxic Threat Nerve Agents on Mammalian Thermoregulation: Effects of Cholinergic Stimulation on Body Temperature Maintenance and Neuroendocrine Responding in Rats Maintained at Different Environmental Temperatures

摘要

This project was designed to develop and validate a model system for determining the effects of acetylcholinesterase inhibitors (AChEI) on a variety of neuroendocrine and biochemical parameters in rats exposed to various environmental temperatures. The model system would be developed using the reversible AChEI physostigmine, then validated with the irreversible AChEI, Soman. Standard procedures for measurement of the neuroendocrine and biochemical parameters (body temperature, plasma corticosterone, fatty acids, and glucose, plasma, erythrocyte and brain AChE, and oxygen consumption/carbon dioxide production) are being used. Data presented in this report indicate that the proposed model system is valid for determining the interactive effects of AChEI with various response systems at several environmental temperatures. Only in those rats in which brain AChE activity was inhibited by >40-50% did a hypothermia and elevation of plasma levels of corticosterone and glucose occur; plasma fatty acids were not elevated. A variety of drug interactions with physostigmine were examined. Centrally-acting cholinergic blockers were the most-effective antagonists. Other drugs had mixed effects. (AW)