Developmental and endocrine impacts of early-life exposures to venlafaxine in fish
Bibliographic record
Abstract
Ubiquitous use of antidepressants has led to marked increases in the concentrations of these pharmaceuticals in the environment. Venlafaxine, a selective serotonin and norepinephrine, and at high concentrations dopamine, reuptake inhibitor, is commonly found at parts per billion concentrations in surface waters. Little is known about the effects of this compound on non-target organisms, such as fish, with a gap of knowledge on the impacts of early-life exposures. In this study, the overarching hypothesis tested was that developmental venlafaxine exposure disrupts neurodevelopment, leading to acute and chronic impacts of the endocrine system of fish. The results reveal for the first time that the deposition of venlafaxine in zebrafish embryos (Danio rerio) affects early development. Venlafaxine exposure led to accelerated embryogenesis, and disrupts neurogenesis, demonstrating the capacity of the antidepressant to disrupt neurodevelopment. Investigations into the targets of venlafaxine impact suggest that the development of the serotonergic and noradrenergic systems are disrupted, with the compound reducing early serotonin immunoreactivity and catecholamine cell number. Exposed zebrafish larvae exhibit depressed activity, and this was due to reduced serotonin content, as recovery of serotonin immunoreactivity by concurrent injections of this monoamine rescues behavioural phenotypes in venlafaxine exposed larvae. Zygotic venlafaxine exposure also imparts long-term perturbations in zebrafish endocrine responses, including the attenuation of the acute stressor-induced cortisol levels of adult females, and growth reduction through disruptions in the function of the growth hormone-insulin-like growth factor axis in juveniles. I also conducted a study with fathead minnows (Pimephales promelas), an ecotoxicologically-relevant species in Canadian waterways, and found that early-life exposure to environmentally-relevant levels of venlafaxine reduces both activity and growth. This thesis revealed that early monoaminergic systems are heavily afflicted by zygotic venlafaxine deposition, and this may be a mode of action by which venlafaxine disrupts behavioural responses. Overall, venlafaxine is an endocrine disruptor, altering larval behavioural responses, perturbing the highly conserved stress response, and impacting early developmental growth. These changes in function may reduce the fitness of fish in waterways, and the results obtained here will provide critical biomarkers and phenotypes of disruption due to venlafaxine exposure for environmental risk assessment in aquatic habitats.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".