The influence of acute dopamine transporter inhibition on manic-, depressive-like phenotypes, and brain oxidative status in adult zebrafish.

Functional changes in dopamine transporter (DAT) are related to various psychiatric conditions, including bipolar disorder (BD) symptoms. In experimental research, the inhibition of DAT induces behavioral alterations that recapitulate symptoms found in BD patients, including mania and depressive mood. Thus, developing novel animal models that mimic BD-related conditions by pharmacologically modulating the dopaminergic signaling is relevant. The zebrafish (Danio rerio) has been considered a suitable vertebrate system for modeling BD-like responses, due to the well-characterized behavioral responses and evolutionarily conservation of the dopaminergic system of this species. Here, we investigate whether GBR 12909, a selective inhibitor of DAT, causes neurobehavioral alterations in zebrafish similar to those observed in BD patients. Behaviors were recorded after a single intraperitoneal (i.p.) administration of GBR 12909 at different doses (3.75, 7.5, 15 and 30 mg/kg). To observe temporal effects on behavior, swim path parameters were measured immediately after the administration period during 30 min. Locomotion, anxiety-like behavior, social preference, aggression, despair-like behavior, and oxidative stress-related biomarkers in the brain were measured 30 min post administration. GBR 12909 induced prominent effects on locomotor activity and vertical exploration during the 30-min period. Hyperactivity was observed in GBR 30 group after 25 min, while all doses markedly reduced vertical drifts. GBR 12909 elicited hyperlocomotion, anxiety-like behavior, decreased social preference, aggression, and induced depressive-like behavior in a behavioral despair task. Depending on the dose, GBR 12909 also decreased SOD activity and TBARS levels, as well as increased GR activity and NPSH content. Collectively, our novel findings show that a single GBR 12909 administration evokes neurobehavioral changes that recapitulate manic- and depressive-like states observed in rodents, fostering the use of zebrafish models to explore BD-like responses in translational neuroscience research.

Embryonic Development Effects of Basagran® Herbicide in Danio Rerio: A Preliminary Study.

Bentazon (Basagran®) belongs to the chemical group of benzothiadiazinones. Thus, this study aimed to estimate the influence of herbicide bentazon (3 µg.L-1, 6 µg.L-1, 12 µg.L-1, 300 µg.L-1) in Danio rerio embryos development. The study tested environmental relevant concentrations of bentazon as well as the limit established for drinking water (300 µg.L-1) in Brazil. We performed behavioral and developmental analyzes during 96 h of exposure. The bentazon measurements after experimental period showed reduction ranging from 5.0 to 18.93% between exposed groups. Our results showed significant differences in the heart rate, which was significantly higher in groups exposed to all bentazon concentrations compared to control groups. The absence of alterations in the behavioral parameters showing that the herbicide bentazon at the concentrations tested had few adverse effects on the development and behavior of the Danio rerio embryos. Considering the toxic point of view, there is a chance that bentazon acts together with other environmental contaminants as an additive or synergistic way.

Glyphosate-based herbicide (GBH) causes damage in embryo-larval stages of zebrafish (Danio rerio).

Glyphosate-Based Herbicides (GBH) show risks to the environment and also to aquatic organisms, such as fish. The present work aimed to evaluate the effects of GBH and Pure Glyphosate (PG) exposure on Danio rerio embryos at drinking water concentrations. Zebrafish embryos were exposed to 250, 500, and 1000 µg L-1 of Roundup Original DI® and pure glyphosate for 96 h. Glyphosate concentration in water, parameters physicochemical water, survival, hatching rate, heart rate, malformations, behavior, and biomarkers were evaluated. We verified that at 6 h post-fertilization (hpf), animals exposed to GBH 500 showed decreased survival as compared to the control. The hatching rate increased in all groups exposed to GBH at 48 hpf as compared to the control group. The embryos exposed did not present changes in the spontaneous movement and touch response. Exposed groups to GBH demonstrated a higher number of malformations in fish embryos as compared to the control. Most malformations were: pericardial edema, yolk sac edema, body malformations, and curvature of the spine. In heart rate, bradycardia occurred in groups exposed, as predicted due to cardiac abnormalities. As biochemical endpoints, we observed a decrease in Glutathione S-transferase (GBH 250, GBH 500 and PG 250) and Acetylcholinesterase (GBH 250 and PG 250) activity. No differences were found between the groups in the concentration of protein, Total Antioxidant Capacity Against Peroxyl Radicals, Lipid peroxidation, Reactive Oxygen Species, Non-protein thiols, and Catalase. In conclusion, the damage in all evaluated stages of development was aggravated by survival and malformations. Therefore, the large-scale use of GBHs, coupled with the permissiveness of its presence could be the cause damage to the aquatic environment affecting the embryonic development of non-target organisms.

Effects of glyphosate on zebrafish: a systematic review and meta-analysis.

Glyphosate herbicide is widely used in worldwide crop production. Consequently, its active ingredient, surfactants, and adjuvants commonly reach the aquatic ecosystem, thereby harming the biota. An investigation into how this herbicide affects aquatic species is important, especially in fish, as they have the ability to absorb and concentrate toxins. We aimed to evaluate the effects of glyphosate on the embryonic, larval and adult stages of zebrafish (Danio rerio), an appreciable organismal model. In this sense, we performed a meta-analysis using published articles from online databases (PubMed and ScienceDirect), which covered studies published until 2022. From a massive compilation of studies evaluating the effects of active substance glyphosate and Glyphosate-Based Herbicides (GBH) on zebrafish, we selected 36 studies used in downstream analyses. Overall, we report that glyphosate affects developmental stages and demonstrates toxicity and damage in zebrafish. We observed that embryos exposed to glyphosate exhibit increased mortality. There was also an increase in the number of morphological abnormalities related to yolk sac oedema, pericardial oedema, spinal curvature and body malformations, and a decrease in body size was observed. Furthermore, there was a decrease in the number of beats. The biochemical results demonstrated an increase in reactive oxygen species and antioxidant capacity against peroxyl radicals in the gills. The literature shows that glyphosate decreased the distance covered and the mean speed of the animals and increased the number of rotations. We concluded that glyphosate causes damage in the embryonic, larval and adult stages of this species. These results are valid for zebrafish and can be applied to other freshwater fish species. Graphical abstract.