A. Figueroa-Pérez, M. Cáceres-Chacón, S. Rodríguez-Rosado, G. Hernández-Busot, H. Haddock-Martínez,

M. Rivera-López, O. Martínez-Guzmán, D. Sierra-Mercado

Dept. of Anatomy and Neurobiology., University of Puerto Rico School of Medicine, San Juan, PR

Glyphosate is the most common active ingredient in herbicides used in landscaping and agriculture. Glyphosate is thought to be safe for humans and animals because it acts by inhibiting a metabolic route almost exclusive to plants. However, recent studies in rodents have shown that glyphosate at either high or low doses can increase the expression of anxiety-like behaviors.

Moreover, studies have shown that emotional states influence how novel stimuli are interpreted.

High levels of anxiety may lead to more negative valence or threatening responses to otherwise neutral novel stimuli. The effect of glyphosate on threat responses to novelty has not been assessed. Therefore, we aimed to evaluate the effect of prolonged oral consumption of glyphosate-contaminated drinking water on threat response to novelty. To achieve this, rats were treated with a target dose of 2.0mg/kg of glyphosate daily (chronic references dose approved by the E.P.A.) in their drinking water. Control rats were treated in the same manner but received filtered drinking water. After 10 weeks of exposure, we assessed for anxiety-like behavior in the elevated plus maze. Here, glyphosate decreased the time spent in the open arms (glyphosate: 48.95, control: 103.7; p=0.0125). After an additional 4 weeks of exposure, animals were assessed for time interacting with a novel object as an index of threat response. Here, glyphosate-treated rats spent less time exploring the novel object (glyphosate: 44.35, control: 89.69; p = 0.0365).

Lastly, after 16 weeks of exposure, animals were exposed to 5 repetitions of a novel auditory tone (30s, 4kHz, 77dB; 3 min intertrial interval) within a familiar context to further explorer threat response. A threat response was measured as time spent freezing during the tone. We observed that glyphosate increased overall freezing to a novel tone (glyphosate: 14.05, control: 4.949; p = 0.0201). For these reasons, it appears that glyphosate exposure increases threat responses to different types of neutral, novel stimuli. Future directions include evaluating brain regions involved in anxiety-like behaviors for changes in neuronal activity.

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