Regulation of neuroendocrine parameters following physostigmine and soman intoxication at varying environmental temperatures in the rat
Abstract
The possible role(s) of cholinergic system(s) in the regulation of body temperature is of significance to military personnel and civilians who may be exposed to a sub-lethal dose of a toxic nerve agent (i.e. soman). The objectives of this project center on an assessment of the various components associated with the control of thermoregulation. The reversible acetylcholinesterase (AChE) inhibitor physostigmine and the highly toxic irreversible AChE inhibitor soman were used to assess the role of cholinergic system(s) on thermoregulation by determination of: (1) body temperature, (2) acetylcholinesterase activity, and (3) neuroendocrine parameters in animals exposed to various environmental temperatures. The neuroendocrine parameters measured include plasma corticosterone (PCS), plasma fatty acids (PFA), and plasma glucose (PGL). Body temperature was assessed, as well as central (brain) and peripheral (plasma and erythrocyte) AChE activity over a 96 hour period. Drug interactions were utilized to further delineate the roles of various neuronal systems. The results obtained should aid in developing therapeutic regimens for use in treatment of AChE inhibitor poisoning with organophosphates. Reversible AChE inhibition (physostigmine) caused an hypothermia of short duration, while irreversible inhibition (soman) failed to produce a consistent hypothermia. Physostigmine increased plasma corticosterone and plasma glucose levels, while soman had minimal effects on plasma corticosterone and plasma glucose levels, but generally lowered plasma fatty acid levels. Differences also exist in the effects of the agents on central and peripheral AChE activity. Physostigmine significantly inhibited brain AChE activity, with lesser effects on plasma and erythrocyte AChE activity, while soman had an opposite effect. These and results from drug interaction studies suggest that physostigmine is able to cross the blood-brain barrier readily, while soman is not, and that the hypothermia as well as plasma corticosterone and plasma glucose levels appear to be mediated by central cholinergic component involving muscarinic receptors. Therefore, physostigmine is a poor model agent for examining the effects of the organophosphate agent soman on thermoregulatory processes.
Degree
Ph.D.
Advisors
Maickel, Purdue University.
Subject Area
Pharmacology
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