Interactive Effects of Venlafaxine and Thermal Stress on Zebrafish (Danio rerio) Inflammatory and Heat Shock Responses

Venlafaxine (VFX), a commonly prescribed antidepressant often detected in wastewater effluent, and acute temperature elevations from climate change and increased urbanization, are two environmental stressors currently placing freshwater ecosystems at risk. This study focused on understanding if exposure to VFX impacts the agitation temperature (T ag ) and critical thermal maximum (CT max ) of zebrafish ( Danio rerio ). Additionally, we examined the interactive effects of VFX and acute thermal stress on zebrafish heat shock and inflammatory immune responses. A 96 hour 1.0 μg/L VFX exposure experiment was conducted, followed by assessment of thermal tolerance via CT max challenge. Heat shock proteins and pro-inflammatory immune cytokines were quantified through gene expression analysis by quantitative PCR (qPCR) on hsp 70, hsp 90, hsp 47, il-8, tnfα , and il-1β within gill and liver tissue. No significant changes in agitation temperature between control and exposed fish were observed, nor were there any differences in CT max based on treatment. Unsurprisingly, hsp 47, 70, and 90 were all upregulated in groups exposed solely to CT max , while only hsp 47 within gill tissue showed signs of interactive effects, which was significantly decreased in fish exposed to both VFX and CT max . No induction of an inflammatory response occurred. This study demonstrated that environmentally relevant concentrations of VFX have no impact on thermal tolerance performance in zebrafish. However, VFX is capable of causing diminished function of protective heat shock mechanisms, which could be detrimental to freshwater fish populations and aquatic ecosystems as temperature spikes become more frequent from climate change and urbanization near watersheds. Summary Statement This study predicts the effects that climate change and anthropogenic pollutants may have on fish ability to tolerate elevated temperatures, and examines the physiologic challenges these stressors may introduce.