Biology subjects

Bastos, L. M.

Publications and source records attributed to Bastos, L. M..

13 recordsLinked to original sources

bioRxiv2026

Unpredictable chronic stress redistributes novelty-evoked exploratory space use and yields method-dependent identification of resilient-like archetypes in zebrafish

Unpredictable chronic stress (UCS) produces heterogeneous behavioural outcomes, but identifying resilient individuals remains challenging because post-stress behaviour is multidimensional and classification depends on the analytical framework. We characterised novelty-evoked exploration in 178 adult zebrafish (89 unstressed reference, 89 UCS-exposed) using four Novel Tank Test variables: distance travelled, line crossings, upper-zone entries and upper-zone time, from a historical LAPCOM dataset from four independent cohorts. Behaviour was robustly normalised to control distributions within cohorts. In the unstressed population, principal component analysis revealed a dominant exploratory gradient (PC1 = 74.9%; PC2 = 18.7%), whereas weighted k-nearest-neighbour Louvain analysis yielded a stable two-profile partition. However, null-model inference and resampling did not support discrete behavioural populations, indicating a predominantly continuous reference architecture. UCS significantly redistributed individuals within this architecture (PERMANOVA: F(1,173) = 8.10, R2= 0.0423, p = 0.0016), reducing occupancy of the higher-exploration reference profile from 55.1% to 24.7%, while multivariate dispersion, Mahalanobis distance and global correlation structure showed no detectable differences. De novo Louvain analysis identified lower- and higher-exploration configurations, but correspondence with the control reference was asymmetric: all 44 lower-exploration fish mapped to the lower reference profile, whereas only 22 of 45 higher-exploration fish mapped to the higher reference profile. Thus, higher exploration after UCS was insufficient to define a resilient-like response. Across five analytical frameworks, resilient assignments ranged from 9 to 45 individuals and susceptible assignments from 23 to 68, with partial individual-level convergence. These findings support reference-integrated behavioural stratification for identifying resilient- and susceptible-like candidates for physiological, cellular and molecular validation.

neuroscience↗

bioRxiv2026

Modulation of social behavior in adult zebrafish (Danio rerio): a systematic review and meta-analysis

Social behavior is a fundamental phenotype across vertebrates. Zebrafish (Danio rerio) have emerged as a valuable translational model for investigating the neurobiological mechanisms underlying sociability, particularly due to their robust shoaling behavior and experimental tractability. However, the literature presents issues of reproducibility and inconsistent findings regarding the modulation of social preference and shoal cohesion in adult zebrafish. We conducted a systematic review and meta-analysis to synthesize studies evaluating the effects of pharmacological interventions that modulate the central nervous system and stress-related interventions on social behavior in adult zebrafish and, when available, anxiety-like behavior. The literature search was performed in three databases (Embase, PubMed, and Web of Science), followed by a two-step screening process based on inclusion/exclusion criteria. The included studies underwent extraction of qualitative and quantitative data, as well as risk of bias assessment. Interventions from the included studies (n = 108) were categorized according to their nature, mechanism of action, and/or therapeutic purpose, resulting in seven, four, and five meta-analyses for social preference, shoal cohesion, and anxiety-related tests, respectively. Ethanol, NMDA antagonists, pro-dopaminergic agents, and stress-related interventions decreased social preference, while stress-related interventions increased shoal cohesion. The fact that stress produced opposite effects suggests that these paradigms measure distinct sociability constructs, or perhaps are differentially modulated by confounding factors, like anxiety for example. The studies presented high heterogeneity, with prediction intervals compatible with effects in both directions, as well as methodological limitations and deficiencies in data reporting, as evidenced by the risk of bias assessment. These findings emphasize the need for well-designed new studies to validate the findings and expand the evidence on interventions that currently lack sufficient studies for quantitative synthesis.

neuroscience↗

bioRxiv2026

Effects of NMDA antagonists on social behaviour: a systematic review and meta-analysis of preclinical studies

Social withdrawal is a key component of the negative symptom domain of schizophrenia, and pharmacological blockade of the N-methyl-D-aspartate receptor (NMDAR) is widely used to model schizophrenia-relevant phenotypes in animals. However, findings on social behaviour are inconsistent across paradigms and laboratories. We therefore conducted a systematic review and meta-analysis to synthesise the effects of dizocilpine, ketamine, and phencyclidine on social interaction and social preference, to evaluate whether clinically approved antipsychotics modify these outcomes, and to examine locomotor activity measured within the same social tests to aid interpretation. We searched Embase, PubMed and Web of Science without language or date restrictions. Controlled in vivo studies in laboratory animals administering an eligible NMDAR antagonist and reporting social interaction and/or social preference outcomes were included. Two reviewers independently screened records, extracted data and assessed risk of bias. Effect sizes were computed as standardised mean differences and synthesised using correlated multilevel random-effects models with cluster-robust variance estimation. In total, 264 studies met the inclusion criteria. Overall, NMDAR antagonists were associated with reduced social interaction and reduced social preference relative to controls, although the social preference literature appeared vulnerable to small-study effects and imprecision. Locomotor activity measured during social interaction tests tended to be higher following NMDAR antagonists, whereas during social preference no consistent overall change was observed. In animals exposed to NMDAR antagonists, antipsychotics increased social behaviour, but these changes commonly co-occurred with reduced locomotion during social interaction tests, suggesting that improvements in social measures may partly reflect altered behavioural competition and time allocation rather than selective restoration of social functioning. Taken together, the evidence supports an overall link between NMDAR antagonism and reduced social behaviour, but the strength and interpretability of this signal depend on the paradigm and are constrained by heterogeneity and limitations in reporting.

pharmacology and toxicology↗

bioRxiv2025

Unpredictable chronic stress does not alter social behavior in zebrafish

Stress-related disorders encompass diverse behavioral alterations, including impaired social functioning. The zebrafish (Danio rerio) is a valuable model for studying these phenomena, particularly because of its robust and ethologically conserved social behaviors. Unpredictable chronic stress (UCS) produces behavioral, physiological, and molecular changes in zebrafish that parallel core features of human anxiety and depressive disorders; however, its impact on social outcomes remains unclear. Here, we examined whether a 14-day UCS protocol alters social behavior in adult zebrafish using two complementary assays: the social preference test and the shoal cohesion test. Across two independent experiments, UCS did not elicit detectable changes in individual social approach or group-level cohesion. In contrast, UCS induced clear anxiety-like behavior in the novel tank test, validating the stress manipulation, with stressed fish displaying reduced vertical exploration and decreased time in the upper zone. Shoal cohesion measures showed a time-dependent decrease in both groups, consistent with habituation to the testing environment rather than a stress-specific effect. Together, these results suggest that social behavior in adult zebrafish is relatively resilient to UCS under the conditions tested, whereas anxiety-like responses are markedly affected. Future work should investigate whether factors such as stressor intensity, developmental stage, sex composition, or social hierarchy modulate the sensitivity of social behavior to chronic stress.

neuroscience↗

bioRxiv2025

Ketamine-induced NMDA receptor hypofunction alters social and locomotor behavior in adult zebrafish

BackgroundNMDA receptor antagonists, such as ketamine, are widely used to model schizophrenia-related phenotypes in preclinical studies. While zebrafish have emerged as a promising model organism for neuropsychiatric research, few studies have characterized their behavioral responses to repeated ketamine exposure. MethodsThree independent experiments were conducted to evaluate the acute, repeated and sustained behavioral effects of ketamine in adult zebrafish. In Experiment I, fish were exposed to 10, 20, or 40 mg/L ketamine once daily for five days, and submitted to the social preference (SPT) and open tank (OTT) tests on days 1 and 5, and re-exposed and re-tested on day 7 after a 48-hour washout. Experiments II and III assessed whether behavioral changes persisted following 5- or 14-day exposure protocols, with testing conducted 48 hours after the final treatment. ResultsKetamine induced robust, concentration-dependent alterations in Experiment I: it reduced social interaction and increased locomotor activity in the SPT on all experimental days, while increased rotational behavior in the OTT on days 1 and 5. These effects did not intensify over repeated exposure and were not sustained after a 48-hour washout in either protocol (Experiments II and III). ConclusionsThe results support the utility of zebrafish for modeling acute behavioral responses to NMDA receptor antagonism, capturing features of schizophrenia-like phenotypes. However, no evidence of behavioral sensitization or lasting disruption was observed, diverging from rodent studies. Future studies should incorporate antipsychotic validation, neurochemical analyses, and alternative exposure strategies to further develop zebrafish as a translational model for psychiatric research.

pharmacology and toxicology↗

bioRxiv2025

Linalool and trans-nerolidol prevent pentylenetetrazole-induced seizures in adult zebrafish

BackgroundLinalool (LIN) and trans-nerolidol (NER) are terpene alcohols found in plant-derived essential oils commonly used in traditional systems of medicine. Both compounds have shown antiseizure, sedative, and antioxidant effects in rodent and in vitro models. Due to their structural similarity, a comparative evaluation of their antiseizure profiles is warranted. This study examined the effects of acute LIN and NER exposure in a pentylenetetrazole (PTZ)-induced seizure model in zebrafish (Danio rerio). MethodsA total of 240 adult zebrafish were randomly assigned to the following groups: blank control (dechlorinated water), vehicle control (1% DMSO), positive control (50 {micro}M diazepam, DZP), and three concentrations of LIN or NER (4, 40, 400 {micro}M). Fish were exposed to treatments for 10 minutes, transferred to a washout beaker with dechlorinated water for 5 minutes, and then transferred to PTZ (10 mM) for 20-minute behavioral recording. Seizure activity was scored by blinded observers (BORIS(R)), and locomotion was analyzed with ANY-maze software. ResultsLIN at 400 {micro}M and NER at 40 and 400 {micro}M significantly prolonged latency to clonic- and tonic-like seizures and reduced seizure severity. Notably, 400 {micro}M NER exceeded DZP in effect size, and 40 {micro}M NER also enhanced locomotor activity. ConclusionLIN and NER delayed progression to severe seizure stages and reduced seizure severity, supporting their antiseizure potential. NER consistently outperformed LIN, demonstrating stronger efficacy than DZP at the highest concentration. Consistent with rodent studies, these findings position both as promising leads for drug development.

neuroscience↗

bioRxiv2024

Evaluation of behavioral and neurochemical changes induced by carbofuran in zebrafish (Danio rerio)

Carbofuran (CF) is a carbamate class pesticide, widely used in agriculture for pest control in crops. On the other hand, CF is also detected as a contaminant in food and water sources. This pesticide has high toxicity in non-target organisms, and its presence in the environment poses a threat to the ecosystem. Research has revealed that this pesticide acts as an inhibitor of acetylcholinesterase (AChE), inducing an accumulation of acetylcholine in the brain. Consequently, this leads to the emergence of a cholinergic syndrome and various detrimental effects on human health. Nonetheless, our understanding of CF impact on the central nervous system remains elusive. Therefore, this study aimed to investigate the effects of CF on behavioral and neurochemical parameters in adult zebrafish. The animals were exposed for 96 hours to different concentrations of CF (5, 50, and 500 {micro}g/L) and subjected to behavioral assessments in the novel tank test (NTT) and social preference test (SPT). Subsequently, they were euthanized, and their brains were used to evaluate neurochemical markers associated with oxidative stress and AChE levels. In the NTT and SPT, CF did not alter the evaluated behavioral parameters. Furthermore, CF did not affect the levels of AChE, non-protein sulfhydryl groups, and thiobarbituric acid reactive species in the zebrafish brain. However, further research is needed regarding the environmental exposure of this compound to non-target organisms.

neuroscience↗

bioRxiv2024

Exposure to epoxiconazole induces hyperlocomotion in adult zebrafish

Global agricultural production is sustained by an elevated use of pesticides. Their application in crops results in environmental contamination, which is demonstrated by widespread detections of these chemicals in aquatic ecosystems. This presence poses a risk to non-target organisms and ecological balance since the effects of potential exposure are misunderstood. Epoxiconazole (EPX) is a widely employed triazole fungicide, which has been frequently reported as a contaminant in superficial waters. However, the behavioral effects of EPX exposure in non-target organisms such as fish remain unexplored. We aimed to investigate the effects of EPX exposure on behavioral and biochemical outcomes, using zebrafish as a model organism. For this purpose, a static system was set with concentrations (24, 144, 240 g/L) based on the fungicide environmental detection. The novel tank test (NTT) was performed after 96 h of exposure. The social preference test (SPT) was executed after 120 h, as well as the biochemical assays. In the NTT, the animals increased distance traveled, crossings, entries in the top area, and mean speed, indicating hyperlocomotion. No significant effects were observed in the SPT and the biochemical analyses. We suggest that the increased locomotion is related to the stimulant properties of EPX. Our results contribute to an in-depth understanding of this fungicide effects in zebrafish, which is essential for environmental contamination monitoring and management.

neuroscience↗

bioRxiv2023

Neurobehavioral effects of fungicides in zebrafish: a systematic review and meta-analysis

With the aim of yielding high productivity levels, pesticides are widely used in global agriculture. Among them, fungicides are compounds intended to inhibit fungal proliferation in crops and seeds. Their application often leads to environmental contamination, with these chemicals persistently being detected in surface waters. This presence may threaten non-target organisms that dwell in the affected ecosystems, including humans. In toxicologic research, the zebrafish (Danio rerio) is the most used fish species to assess the potential effects of fungicide exposure, generating numerous and sometimes conflicting findings. We conducted a systematic review and meta-analysis aiming to synthesize the neurobehavioral effects of fungicides in zebrafish. The search was performed in three databases (PubMed, Scopus, and Web of Science) and the screening was based on a two-stage process guided by pre-defined inclusion/exclusion criteria. Qualitative and quantitative data, as well as reporting quality, were extracted from the included studies (n = 60). Meta-analyses were performed for the outcomes of distance traveled in larvae and adults, and spontaneous movements in embryos. We found an overall significant effect of fungicide exposure on distance, which was lower in exposed versus control groups (SMD -0.44 [-0.74; -0.13], p = 0.0055). No effect was observed for spontaneous movements. The overall heterogeneity for distance and spontaneous movements was considered high (I2 = 80%) and moderate (I2 = 74%), respectively. This can be explained by substantial methodological variation between protocols, whereas a poor reporting practice hinders the proper critical evaluation of the findings. However, a sensitivity analysis did not indicate any study skewing the meta-analyses. This review demonstrates the need for better-designed and reported experiments in this field. Highlights- We systematically reviewed the behavioral effects of fungicides in zebrafish - Fungicides decrease the distance traveled - Fungicide exposure has no significant effects on spontaneous movements - Moderate to high levels of heterogeneity were found - The results showed a need for better-designed studies with clarity of report

pharmacology and toxicology↗

bioRxiv2022

Ten years of unpredictable chronic stress in zebrafish: a systematic review and meta-analysis

The zebrafish (Danio rerio) is a model animal that is being increasingly used in neuroscience research. A decade ago, the first study on unpredictable chronic stress (UCS) in zebrafish was published, inspired by protocols established for rodents in the early 1980s. Since then, several studies have been published by different groups, in some cases with conflicting results. We conducted a systematic review to identify studies evaluating the effects of UCS in zebrafish and meta-analytically synthetized the data of neurobehavioral outcomes and relevant biomarkers. Literature searches were performed in three databases (PubMed, Scopus, and Web of Science) and a two-step screening process based on inclusion/exclusion criteria. The included studies underwent extraction of qualitative and quantitative data, as well as risk of bias assessment. Outcomes of included studies (n = 38) were grouped into anxiety/fear- related behaviour, locomotor function, social behaviour, or cortisol level domains. UCS increased anxiety/fear-related behaviour and cortisol levels while decreased locomotor function, but a significant summary effect was not observed for social behaviour. Despite including a significant number of studies, the high heterogeneity and the methodological and reporting problems evidenced in the risk of bias analysis make it difficult to assess the internal validity of most studies and the overall validity of the model. Our review thus evidences the need to conduct well-designed experiments to better evaluate the effects of UCS on the behaviour of zebrafish.

neuroscience↗

bioRxiv2022

Effects of taurine in mice and zebrafish behavioral assays with translational relevance to schizophrenia

BackgroundAltered redox state and developmental abnormalities in glutamatergic and GABAergic transmission during development are linked to the behavioral changes associated with schizophrenia. As an amino acid that exerts antioxidant and inhibitory actions in the brain, taurine is a potential candidate to modulate biological targets relevant to this disorder. Here, we investigated in mice and zebrafish assays whether taurine prevents the behavioral changes induced by acute administration of MK-801 (dizocilpine), a glutamate NMDA receptor antagonist. MethodsC57BL/6 mice were intraperitoneally administered with saline or taurine (50, 100 and 200 mg/kg) followed by MK-801 (0.15 mg/kg). Locomotor activity, social interaction and prepulse inhibition of the acoustic startle reflex were then assessed in different sets of animals. Zebrafish were exposed to tank water or taurine (42, 150 and 400 mg/L) followed by MK-801 (5 M); social interaction and locomotor activity were evaluated in the same test. ResultsMK-801 induced hyperlocomotion and disrupted sensorimotor gating in mice; in zebrafish, it reduced sociability while increased locomotion. Taurine was mostly devoid of effects and did not counteract NMDA antagonism in mice or zebrafish. DiscussionContradicting previous clinical and preclinical data, taurine did not show antipsychotic-like effects in the present study. However, it still warrants consideration as a preventive intervention in animal models of relevance to the prodromal phase of schizophrenia; further studies are thus necessary to evaluate whether and how taurine might benefit patients.

pharmacology and toxicology↗

bioRxiv2021

Micronized curcumin causes hyperlocomotion in zebrafish larvae

Zebrafish larvae have been widely used in neuroscience and drug research and development. In the larval stage, zebrafish present a broad behavioral repertoire and physiological responses similar to adults. Curcumin (CUR), a major component of Curcuma longa L. (Zingiberaceae), has demonstrated the ability to modulate several neurobiological processes relevant to mental disorders in animal models. However, the low bioavailability of this compound can compromise its in vivo biological potential. Interestingly, it has been shown that micronization can increase the biological effects of several compounds. Thus, in this study, we compared the effects of acute exposure for 30 minutes to the following solutions: water (control), 0.1% DMSO (vehicle), 1 M CUR, or 1 M micronized curcumin (MC) in zebrafish larvae 7 days post-fertilization (dpf). We analyzed locomotor activity (open tank test), anxiety (light/dark test), and avoidance behavior (aversive stimulus test). Moreover, we evaluated parameters of oxidative status (thiobarbituric acid reactive substances and non-protein thiols levels). MC increased the total distance traveled and absolute turn angle in the open tank test. There were no significant differences in the other behavioral or neurochemical outcomes. The increase in locomotion induced by MC may be associated with a stimulant effect on the central nervous system, which was evidenced by the micronization process.

neuroscience↗

bioRxiv2021

Ochratoxin A induces behavioral and neurochemical changes in adult zebrafish

Ochratoxin A (OTA) is a mycotoxin produced by species of filamentous fungi widely found as a contaminant in food and with high toxic potential. Studies have shown that this toxin cause kidney and liver damage, however, data on the effects of exposure to OTA on the central nervous system are still scarce. Zebrafish (Danio rerio) is a teleost often used in translational research due to its physiological, genetic, and behavioral homology with mammals, in addition to being useful as an environmental bioindicator. Thus, this study aimed to investigate the effects of exposure to OTA on behavioral and neurochemical parameters in adult zebrafish. The animals were treated with different doses of OTA (1.38, 2.77, and 5.53 mg/kg) and submitted to behavioral evaluations in the open tank and social interaction tests. Subsequently, they were euthanized, and the brains were used to assess markers associated with oxidative status. In the open tank test OTA induced changes in distance, absolute turn angle, mean speed, and time-freezing. However, no significant effects were observed in the social interaction test. Moreover, OTA also induced alterations in neurochemical parameters with changes in non-protein thiols (NPSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). This study showed that OTA can affect neurobiological aspects in zebrafish even at low doses.

neuroscience↗