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oai:figshare.com:article/34034902 2026-09-30T17:28:53Z category_15 category_734 category_106 category_122 portal_5 item_type_1 month_year_09_2026

High-dose/low-stress exposure does not alter body weight or cognition but appears to reduce anxiety in rats. Rashelle Lashley (7302038) Joshua Brian Foster (20175776) Xueqin Wang (350340) Albert John Muhleman (20175779) Samuel Weaver (1344039) Edison Lin (25145140) Liching Lai (25145143) Chien-liang Glenn Lin (16856919) Neuroscience Biological Sciences not elsewhere classified Science Policy Mental Health related chemical agents investigational compound designed including chronic pain improve translational rigor robust behavioral phenotypes like behavioral phenotypes standardize animal models harlan involving exposure experimental conditions evaluated gulf war illness male sd rats experimental conditions behavioral assessments gulf war exposure paradigms animal sources rats using rats may subsequently modified stress levels rat model psychological stress original objective neuropsychiatric symptoms mood problems mild stress initially attempted continued efforts cognitive impairment better interpret Rats were exposed to a high dose of chemical agents and a low-stress protocol for five weeks. Body weight was monitored during GW exposure. At 4−5 weeks post-exposure, rats received either LH-001 or vehicle. Anxiety-like and cognitive behaviors were assessed starting from 8–9 weeks post-exposure. A two-way ANOVA was used for body weight analysis. A one-way ANOVA was used for behavioral analysis. (A) Body weight. Body weights were monitored weekly over the first four weeks (n = 8 for control and n = 16 for GWI). No significant differences were found between groups. (B, C) Open field test. Time spent in the center (B) and total distance traveled (C) were measured (n = 12/group). No significant differences were found between groups. (D) Elevated plus maze test. The percentage of time spent in the open arms was analyzed (n = 8/group). No significant differences were found between groups. (E-F) Dark and light test. Latency to enter the dark chamber (E) and percent of time spent in the light chamber (F) were assessed (n = 8–15/group). GWI/vehicle rats spent significantly more time in the light area; GWI/LH-001 rats also spent more time in the light area but did not reach significance. (G-H) Novelty-suppressed feeding test. Amount of food consumed (G) and latency to begin feeding (H) were analyzed (n = 11–12/group). GWI/LH-001 rats ate significantly more food than control/vehicle rats; GWI/vehicle rats also ate more food but did not reach significance. Overall, high-dose/low-stress exposure appeared to reduce anxiety. (I, J) Recognition memory test. Discrimination index scores for novel object location (I) and novel object recognition (J) were calculated (n = 8/group). No significant differences were found between groups. (K-L) Barnes maze test. Latency to find the escape hole (K) and time spent in the target quadrant (L) during the initial training phase were analyzed (n = 8/group). GWI/LH-001 rats spent less time finding the target hole than GWI/vehicle rats. (M-N) Barnes maze re-training. Latency to the new escape hole (M) and time spent in the new target quadrant (N) were analyzed one week later (n = 8/group). No significant differences were found between groups. (O) Barnes maze memory recall. Time spent in the original target quadrant during the re-training phase was analyzed (n = 8/group). GWI/rats spent significantly more time in the target quadrant than control/vehicle rats. Overall, high-dose/low-stress exposure did not cause cognitive issues. *p < 0.05. 2026-09-30T17:28:43Z Image Figure 10.1371/journal.pone.0337157.g002 https://figshare.com/articles/figure/_p_High-dose_low-stress_exposure_does_not_alter_body_weight_or_cognition_but_appears_to_reduce_anxiety_in_rats_p_/34034902 CC BY 4.0