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Interactions between pyridostigmine bromide and stress on glutamatergic neurochemistry: Insights from a rat model of Gulf War Illness.

Authors
  • Macht, V A1, 2
  • Woodruff, J L1, 2
  • Burzynski, H E1
  • Grillo, C A1, 2
  • Reagan, L P1, 2
  • Fadel, J R1, 2
  • 1 University of South Carolina School of Medicine, Department of Pharmacology, Physiology, and Neuroscience, Columbia, SC, 29208, USA.
  • 2 Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC, 29208, USA.
Type
Published Article
Journal
Neurobiology of stress
Publication Date
May 01, 2020
Volume
12
Pages
100210–100210
Identifiers
DOI: 10.1016/j.ynstr.2019.100210
PMID: 32258255
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Pyridostigmine bromide (PB) was administered to soldiers during the first Gulf War as a prophylactic treatment to protect against toxicity in the event of exposure to nerve agents. Although originally thought to pose minimal risk to soldiers, epidemiological studies have since correlated PB administration with the development of a variety of symptoms, including cognitive dysfunction, termed Gulf War Illness (GWI). We previously demonstrated in a rodent model of GWI that central cholinergic responses were altered to various stimuli. In the current study we used in vivo microdialysis to examine how combinations of PB and repeated restraint stress (RRS) altered extracellular glutamate levels in response to an innate immune challenge (lipopolysaccharide; LPS) and an immobilization stress challenge in the prefrontal cortex (PFC) and hippocampus. There were four groups in this study: vehicle non-stressed control (Veh-NSC), vehicle-stressed (Veh-RRS), PB-NSC, and PB-RRS. While LPS decreased glutamate levels in PB-treated rats relative to vehicle-treated rats in the PFC, PB and stress interacted to attenuate LPS-induced decreases in hippocampal glutamate levels. Although immobilization stress increased glutamate in the PFC, glutamate levels in PB-NSC rats failed to recover in the post-stress period relative to vehicle-treated rats. In the hippocampus, PB-stressed rats failed to exhibit habituation of the glutamate response to immobilization stress relative to vehicle-stressed rats. Collectively, these results indicate that PB and stress interacted to produce brain-region specific effects on glutamate neurochemistry, providing insight into the potential mechanisms underlying interactions between the immune system and persistent cognitive dysfunction in veterans with GWI. © 2020 The Authors.

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