ORCID
https://orcid.org/0009-0008-7895-5161
Degree
Bachelor of Science (B.S.)
Major(s)
Microbiology
Document Type
Immediate Open Access
Abstract
Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim of this study is to determine if repeated PB treatment can affect behavior and neural excitation without directly interacting with the brain. This would be possible via the peripheral effects of PB in the gut, which can induce signals through the vagal nerve, causing excitation in regions like the amygdala and thalamus. Rats were administered PB and a control solution orally for 21 days. Behavioral testing was conducted on days 14-19. Various behavioral tests were used to test for anxiety, cognition, spatial memory, and anhedonia. qPCR was performed on the amygdala and thalamus of behavior cohort rats (n=12) and biochemical cohort rats (n=5). c-Fos and BDNF (brain derived neurotrophic factor) levels were measured over the treatment period as measures of neural excitation. Treatment did not affect performance in most of the behavioral tests, though a slight sex-specific anxiolytic effect was observed during the “open field” test. Additionally, qPCR analysis indicated that PB significantly altered BDNF and c-FOS expression regardless of sex, though several sex specific differences in neural excitation were observed. Analysis of the behavioral and biochemical data suggest that PB does influence neural excitation despite not interacting with the brain directly, and may exhibit slight sex-specific effects.
DOI
https://doi.org/10.54718/SSNB1080
Date Defended
4-30-2025
Funding Source
Department of Defense
Thesis Director
Russell Carr
Second Committee Member
Shirley Guo-Ross
Third Committee Member
Matthew Peaple
Recommended Citation
Martin, Noah A., "Assessing the Behavioral Impact of Pyridostigmine Bromide in Rats" (2025). Honors Theses. 143.
https://scholarsjunction.msstate.edu/honorstheses/143
Included in
Animal Experimentation and Research Commons, Behavioral Neurobiology Commons, Biochemistry Commons, Enzymes and Coenzymes Commons, Medicinal Chemistry and Pharmaceutics Commons, Molecular and Cellular Neuroscience Commons, Pharmacology Commons, Toxicology Commons
