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

Publication date: Available online 31 December 2019Source: Neurobiology of StressAuthor(s): V.A. Macht, J.L. Woodruff, H.E. Burzynski, C.A. Grillo, L.P. Reagan, J.R. FadelAbstractPyridostigmine 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 that 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 rela...

Source: Neurobiology of Stress - January 1, 2020 Category: Neuroscience Source Type: research