RESUMO
Environmental contamination by pharmaceuticals from industrial waste and anthropogenic activities poses adverse health effects on non-target organisms. We evaluated the neurobehavioral and biochemical responses accompanying exposure to ecological relevant concentrations of atenolol (0, 0.1, 1.0, and 10 µg/L) for seven uninterrupted days in adult zebrafish (Danio rerio). Atenolol-exposed fish exhibited anxiety-like behavior, characterized by significant bottom-dwelling with marked reduction in vertical exploration. Atenolol-exposed fish exhibited marked increase in the duration and frequency of aggressive events without altering their preference for conspecifics. Biochemical data using brain samples indicated that atenolol disrupted antioxidant enzyme activities and induced oxidative stress. Exposure to atenolol markedly decreased ATP and AMP hydrolysis without affecting ADP hydrolysis and acetylcholinesterase (AChE) activity. Atenolol significantly upregulated tryptophan hydroxylase 1 (tph1) mRNA expression but downregulated brain-derived neurotrophic factor (bdnf) mRNA. Collectively, waterborne atenolol elicits aggressive and anxiety-like responses in adult zebrafish, accompanied by oxidative stress, reduced nucleotide hydrolysis, altered tph1 and bdnf mRNA expression, which may impact the survival and health of fish in aquatic environment.
Assuntos
Atenolol , Comportamento Animal , Estresse Oxidativo , Poluentes Químicos da Água , Peixe-Zebra , Animais , Atenolol/farmacologia , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Triptofano Hidroxilase/metabolismo , Triptofano Hidroxilase/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismoRESUMO
Obsessive-compulsive disorder (OCD) is a chronic and debilitating illness that has been considered a polygenic and multifactorial disorder, challenging effective therapeutic interventions. Although invaluable advances have been obtained from human and rodent studies, several molecular and mechanistic aspects of OCD etiology are still obscure. Thus, the use of non-traditional animal models may foster innovative approaches in this field, aiming to elucidate the underlying mechanisms of disease from an evolutionary perspective. The zebrafish (Danio rerio) has been increasingly considered a powerful organism in translational neuroscience research, especially due to the intrinsic features of the species. Here, we outline target mechanisms of OCD for translational research, and discuss how zebrafish-based models can contribute to explore neurobehavioral aspects resembling those found in OCD. We also identify possible advantages and limitations of potential zebrafish-based models, as well as highlight future directions in both etiological and therapeutic research. Lastly, we reinforce the use of zebrafish as a promising tool to unravel the biological basis of OCD, as well as novel pharmacological therapies in the field.
Assuntos
Modelos Animais de Doenças , Transtorno Obsessivo-Compulsivo , Pesquisa Translacional Biomédica , Peixe-Zebra , Animais , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/genética , Humanos , Comportamento Animal/fisiologiaRESUMO
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.
Assuntos
Mania , Peixe-Zebra , Animais , Humanos , Comportamento Animal , Encéfalo , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Estresse Oxidativo , FenótipoRESUMO
Anxiety is a protective behavior when animals face aversive conditions. The open field test (OFT) is used to assess the spatio-temporal dynamics of exploration, in which both homebase formation and recognition of environmental cues may reflect habituation to unfamiliar conditions. Because emotional- and affective-like states influence exploration patterns and mnemonic aspects, we aimed to verify whether the exploratory behaviors of two zebrafish populations showing distinct baselines of anxiety differ in two OFT sessions. Firstly, we assessed the baseline anxiety-like responses of short fin (SF) and leopard (LEO) populations using the novel tank test (NTT) and light-dark test (LDT) in 6-min trials. Fish were later tested in two consecutive days in the OFT, where the spatial occupancy and exploratory profile were analyzed for 30 min. In general, LEO showed pronounced diving behavior and scototaxis in the NTT and LDT, respectively, in which an "anxiety index" corroborated their exacerbated anxiety-like behavior. In the OFT, the SF population spent less time to establish the homebase in the 1st trial, while only LEO showed a markedly reduction in the latency to homebase formation in the 2nd trial. Both locomotion and homebase-related activities were decreased in the 2nd trial, in which animals also revealed increased occupancy in the center area of the apparatus. Moreover, we verified a significant percentage of homebase conservation for both populations, while only SF showed reduced the number of trips and increased the average length of trips. Principal component analyses revealed that distinct factors accounted for total variances between trials for each population tested. While homebase exploration was reduced in the 2nd trial for SF, an increased occupancy in the center area and hypolocomotion were the main factors that contribute to the effects observed in LEO during re-exposure to the OFT. In conclusion, our novel data support the homebase conservation in zebrafish subjected to independent OFT sessions, as well as corroborate a population-dependent effect on specific behavioral parameters related to exploration.
Assuntos
Comportamento Animal , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Comportamento Animal/fisiologia , Ansiedade , Locomoção , Comportamento Exploratório/fisiologia , FenótipoRESUMO
While pain results from the activation of nociceptors following noxious stimuli, mounting evidence links pain- and stress-related responses in mammals. In zebrafish, the activation of hypothalamic-pituitary-interrenal (HPI) axis may also regulate body pigmentation (the camouflage response). Here, we aimed to investigate a putative relationship between pain-, stress-, and camouflage-related parameters in adult zebrafish. To answer this question, we assessed whether intraperitoneal acetic acid injection can activate the HPI axis, measuring whole-body cortisol and the camouflage response as physiological endpoints in the presence or absence of morphine or naloxone, an opioid antagonist. Acetic acid induced a stereotypic circling behavior in the top of the tank, accompanied by abdominal writhing-like response, a specific phenotype that reflects local nociceptive effect. Both whole-body cortisol levels and camouflage response increased in the acetic acid group, while morphine prevented these responses, and naloxone antagonized morphine-induced effects. Moreover, we observed positive correlations between representative behavioral, physiological and skin coloration endpoints, and a "pain index" was proposed to summarize phenotypic profile of zebrafish under different pharmacological manipulations. Collectively, these findings suggest a coordinated activation of pain, camouflage- and stress-related pathways following acetic acid injection in zebrafish. Our data also support that camouflage response represents a novel and relevant biomarker for future probing pain and stress neurobiology, with a robust sensitivity to opioidergic drugs.
Assuntos
Ácido Acético , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Ácido Acético/toxicidade , Ácido Acético/metabolismo , Hidrocortisona/metabolismo , Naloxona/farmacologia , Naloxona/metabolismo , Morfina/toxicidade , Morfina/metabolismo , Dor , Fenótipo , Mamíferos/metabolismoRESUMO
Stress is a physiological reaction that allows the organisms to cope with challenging situations daily. Thus, elucidating the behavioral outcomes following different stressors is of great importance in translational research. Here, we aimed to characterize the main factors which explain similarities and differences of two stress protocols on zebrafish exploratory activity. To answer this point, we performed behavioral analyses aiming to simplify the data structure associated with homebase-related measurements in an integrated manner. Adult zebrafish were exposed to conspecific alarm substance for 5 min (acute stress protocol - AS) or submitted to 7 days of unpredictable chronic stress (UCS). Immediately after AS or in the subsequent day following UCS (8th day), fish were individually tested in the open field and the behaviors were recorded for 30 min to posterior identification of homebase locations. For both protocols, behavioral clustering revealed two major clusters, grouping homebase- and locomotor-related parameters, respectively. While AS increased both positive and negative correlations between exploratory and locomotor endpoints, a significant increase in negative correlations was found in UCS-challenged fish. Comparison of the principal component analyses data set revealed a reduced exploratory activity using the homebase in AS group, while decreased locomotion in the periphery and anxiety-like behaviors were evidenced in UCS fish. In conclusion, our findings revealed a different structure of behavior in zebrafish following AS and UCS protocols, supporting the existence of distinct behavioral strategies to cope with acute and chronic stress. Furthermore, we expand the use of homebase-related measurements as a valuable tool to investigate complex behavioral modulations in future translational neuropsychiatry research.
Assuntos
Ansiedade , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Comportamento Animal/fisiologia , Atividade Motora/fisiologia , Comportamento Exploratório/fisiologiaRESUMO
The open field is a suitable task to analyze the sequential organization of exploratory activity and the homebase formation represents an important feature of environmental recognition. Although the zebrafish can define homebase locations, there are no data reporting how stressful conditions modulate complex behaviors of this aquatic species in the open field so far. Here, we aimed to characterize the spatio-temporal exploratory activity of adult zebrafish in the open field test, as well as to verify the responsiveness of homebase-related parameters to acute stress (AS) and unpredictable chronic stress (UCS) protocols. Animals were exposed to conspecific alarm substance for 5 min or subjected to a 7-days stress protocol using distinct stressors in an unpredictable manner. Immediately after exposure to AS or 24 h after UCS, fish were individually placed in a circular tank and their behaviors were recorded for 30 min to identify the respective homebase for each animal. We observed that UCS, but not AS, increased thigmotaxis compared to the non-stressed fish. Notably, the sequential organization of exploratory activity showed robust differences depending on the stress protocol. After the first 15 min of trial, AS-challenged fish apparently used the homebase to organize briefly explorations to the environment. Conversely, the UCS group was more immobile in the homebase after periodically performing 'swimming bursts' to the periphery with a greater number of stops per trip. Physiological stress responses were confirmed by the increased whole-body cortisol in both AS and UCS groups. In conclusion, our novel findings report a different exploratory profile related to stress responses in adult zebrafish tested in the open field, supporting the sensitivity of homebase-related parameters to manipulations that modulate affective-like states.
Assuntos
Comportamento Exploratório , Peixe-Zebra , Animais , Comportamento Animal/fisiologia , Comportamento Exploratório/fisiologia , Hidrocortisona , Estresse Fisiológico/fisiologia , Peixe-Zebra/fisiologiaRESUMO
Perfluorooctanoic acid (PFOA) is a contaminant of global concern owing to its prevalent occurrence in aquatic and terrestrial environments with potential hazardous impact on living organisms. Here, we investigated the influence of realistic environmental concentrations of PFOA (0, 0.25, 0.5, or 1.0 mg/L) on relevant behaviors of adult zebrafish (Danio rerio) (e.g., exploration to novelty, social preference, and aggression) and the possible role of PFOA in modulating cholinergic and purinergic signaling in the brain after exposure for 7 consecutive days. PFOA significantly increased geotaxis as well as reduced vertical exploration (a behavioral endpoint for anxiety), and increased the frequency and duration of aggressive episodes without affecting their social preference. Exposure to PFOA did not affect ADP hydrolysis, whereas ATP and AMP hydrolysis were significantly increased at the highest concentration tested. However, AChE activity was markedly decreased in all PFOA-exposed groups when compared with control. In conclusion, PFOA induces aggression and anxiety-like behavior in adult zebrafish and modulates both cholinergic and purinergic signaling biomarkers. These novel data can provide valuable insights into possible health threats related to human activities, demonstrating the utility of adult zebrafish to elucidate how PFOA affects neurobehavioral responses in aquatic organisms.
Assuntos
Fluorocarbonos , Peixe-Zebra , Agressão , Animais , Ansiedade/induzido quimicamente , Caprilatos/toxicidade , Colinérgicos , Fluorocarbonos/toxicidade , Humanos , Peixe-Zebra/fisiologiaRESUMO
Social behaviors are key components that play adaptive roles in various species, including humans. The zebrafish (Danio rerio) is a social species and the shoaling behavior can be pharmacologically manipulated either by anxiogenic or anxiolytic substances, providing translatable data in neuropsychiatric research. Here, we aimed to characterize the shoaling behavior in zebrafish under different pharmacological manipulations in a three-dimensional (3D) perspective using the spatial coordinates of the fish positions. Temporal and spatial reconstructions of shoal occupancy were performed after exposure to conspecific alarm substance (CAS) and caffeine (CAF) (anxiogenic substances) or diazepam (DZP) (a classical anxiolytic drug). Behavioral 3D analyses and spatiotemporal reconstructions of the shoaling behavior revealed that both CAS and CAF decreased the shoal volume, the average fish distance to the centoid point, and increased shoal geotaxis, but only CAS reduced the inter-fish distance when compared to control (CTRL). Conversely, DZP group showed increased shoal volume and inter-fish distance. Because substantial differences were verified when the shoaling response was analyzed in 3D and 2D perspectives, we reinforce the use of 3D reconstructions of fish positions to assess how different manipulations affect the social behavior of zebrafish. The novel procedure described here represents an easy-to-use, inexpensive, and alternative tool to perform a spatiotemporal reconstruction of the shoal occupancy under different pharmacological manipulations, complementing the existing quantification of locomotion activity of multiple fish.