Peripheral ChE Inhibition Modulates Brain Monoamines Levels and c-fos Oncogene in Mice Subjected to a Stress Situation

Abstract

The present study examined, in mice, whether regional patterns of brain monoamines concentrations (DA, 5-HT and their metabolites) and expression of c-Fos protein, that may represent a prolonged functional change in neurons, could be changed after a combined exposure to stress and the peripheral cholinesterase reversible inhibitor pyridostigmine (PYR). Animals were subjected every day to a random combination of mild unescapable electric footshocks and immobilization over a 12-day period, resulting in a significant increase of glucocorticoids levels and an activation of c-fos in hippocampus, thalamus and piriform cortex. This stress protocol induced a significant increase of 5-HT levels in striatum, hippocampus and ponto mesencephalic area (PMA) but failed to induce any DA activation. When PYR (0.2 mg/kg s.c. inducing 19-35% inhibition of the plasmatic ChE activity) was administered twice a day during the last 5 days of the stress session, 5-HIAA levels and expression of c-fos oncogene were significantly increased in the most of the brain areas studied. DA levels were also enhanced in striatum/hippocampus as a result of a possible activation of mesolimbic and nigrostriatal dopamine systems. Taken together, these results suggest that a combined exposure to certain stress conditions and PYR leads, in mice, to functional changes in neurons and may affect centrally controlled functions. The mechanisms underlying these modifications and their behavioral implications remain to be further investigated.

Effects of Repeated Low-dose Soman Exposure on Monoamine Levels in Different Brain Structures in Mice

“…-different responses of serotoninergic system depending on the stress conditions [20][21][22][23][24], but few investigations have been performed on chemical stress such as organophosphorus compound. -a modification of the serotoninergic activity, in the hippocampus, resulting from glucocorticoids [25,26].…”

Chronic stress impacts the cardiovascular system: animal models and clinical outcomes

“…This method places animals in specialized cages that have electrified floors to ensure conduction of the electrical current to the animal's feet. Protocols that differ in terms of intensity, frequency, and duration of electrical shock have been used to induce various degrees of stress (82,274,330,359). Animal behaviors such as predictability or avoidability can influence the magnitude of stress response (37,221,237,360).…”

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“…Chronic stress is also produced by repeating the same treatment for 7-10 days and rats are sacrificed 1 h after the last stress session 15 . Some researchers have modified the method in which rats are subjected to inescapable electric foot shock for 60 minutes (0.15 mA shock, on a variable interval schedule with a mean inter shock interval of 60 seconds) 27 . The biggest advantage of this model is that it effectively produces high degree of stress in the animal.…”