RESUMEN
Chronic treatment with clomipramine, a tricyclic antidepressant drug, reduces symptoms of obsessive-compulsive disorder (OCD) and can influence the activity of the hypothalamic-pituitary-adrenal axis. However, little is known regarding the effects of acute clomipramine on the immediate expression of stress responses. Serotonergic drugs can elicit surfacing, a behavioral profile potentially related to toxicity in fish, although surfacing has not yet been observed after clomipramine exposure. The present study investigated the impact of acute exposure to clomipramine on basal and stress-induced behaviors in the novel tank test and cortisol levels in mixed-sex, wild-type, adult zebrafish (Danio rerio). The findings show clomipramine-exposed groups (regardless of stress exposure) spent much more time in the top of the novel tank and had significantly less overall motor activity in the behavioral task compared to the fish not exposed to the drug. Then, the dose-dependent effects of acute clomipramine on activity in the surface of the novel tank (top third of the top half) were investigated further. Clomipramine dose-dependently increased surface-dwelling and elicited a dose-dependent hypoactivity in overall motor behavior. There were no statistically significant differences in whole-body cortisol levels in either experiment. Like other serotonin-acting drugs, clomipramine strongly elicited surface-dwelling and depressed motor behavior in adult zebrafish. Additional testing is needed to elucidate whether surfacing represents a toxic state and how serotonin regulates surfacing.
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Conducta Animal , Clomipramina , Relación Dosis-Respuesta a Droga , Hidrocortisona , Pez Cebra , Animales , Clomipramina/farmacología , Clomipramina/administración & dosificación , Conducta Animal/efectos de los fármacos , Hidrocortisona/metabolismo , Masculino , Femenino , Antidepresivos Tricíclicos/farmacología , Antidepresivos Tricíclicos/administración & dosificación , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificaciónRESUMEN
BACKGROUND: The dopamine transporter (DAT) is the main regulator of dopamine concentration in the extrasynaptic space. The pharmacological inhibition of the DAT results in a wide spectrum of behavioral manifestations, which have been identified so far in a limited number of species, mostly in rodents. AIM: Here, we used another well-recognized model organism, the zebrafish (Danio rerio), to explore the behavioral effects of GBR 12909, a highly-affine selective DAT blocker. METHODS: We evaluated zebrafish locomotion, novelty-related exploration, spatial cognition, and social phenotypes in the novel tank, habituation and shoaling tests, following acute 20-min water immersion in GBR 12909. RESULTS: Our findings show hypolocomotion, anxiety-like state, and impaired spatial cognition in fish acutely treated with GBR 12909. This behavioral profile generally parallels that of the DAT knockout rodents and zebrafish, and it overlaps with behavioral effects of other DAT-inhibiting drugs of abuse, such as cocaine and D-amphetamine. CONCLUSION: Collectively, our data support the utility of zebrafish in translational studies on DAT targeting neuropharmacology and strongly implicate DAT aberration as an important mechanisms involved in neurological and psychiatric diseases.
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Cocaína , Pez Cebra , Animales , Dopamina , Inhibidores de Captación de Dopamina/farmacología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Cocaína/farmacologíaRESUMEN
Antibiotics have been used for decades to treat various bacterial infections. Apart from bactericidal activities, their potential side effects have not been much studied or evaluated. Neurotoxicity is a major concern in the case of ß-lactam and fluoroquinolone families, which can result in convulsions or seizures. Here, we proposed a hypothesis to check whether antibiotic treatment can conclusively enhance anxiety-like behaviours and how seizure behavioural profile gets modulated in pentylenetetrazole (PTZ)-treated zebrafish. Zebrafish were treated with selected antibiotics such as 25 mg/L Penicillin G (PG) and Ciprofloxacin (CPFX), for 7 days and thereafter exposed to PTZ (7.5 mM) for 20 min. The data indicate that PG and CPFX-treated groups exhibited anxiety-like or stressed behavioural phenotypes in the novel tank test (6 min), and also, they were found to promote hyperactivity. Early onset of PTZ-induced seizure-like behavioural scores, the heightened intensity of seizure and reduced latency in different scores were found in PG and CPFX-administered groups. This study substantiates that PG and CPFX as potential seizure modulators in zebrafish. The zebrafish is a well-established and still expanding model organism in many fields. Here, we again reinforce zebrafish as a prominent model to investigate seizure-like neuro-behavioural entities and confirm that chronic antibiotic use has negative consequences that can exacerbate the circumstances of vertebrate species exhibiting seizure-related reactions.
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Epilepsia , Pez Cebra , Animales , Antibacterianos/toxicidad , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Pentilenotetrazol/toxicidad , Modelos Animales de EnfermedadRESUMEN
Chromone-containing allylmorpholines (CCAMs) are a novel class of compounds that have demonstrated acetyl- and butyryl-cholinesterase-inhibiting and N-methyl-D-aspartate (NMDA) receptor-blocking properties in vitro, but their in vivo pharmacological activity remains underexplored. In this work, we evaluated the psychotropic activity of five different CCAMs (1 (9a), 2 (9j), 3 (9l), 4 (33a), and 5 (33b)) using the novel tank test (NTT) and light/dark box (LDB) test in adult zebrafish. The CCAMs were screened in the NTT at a range of concentrations, and they were found to induce a dose-dependent sedative effect. Compound 4 (33a) was also evaluated using the LDB test, and it was found to have anxiolytic-like properties at low concentrations. To assess the potential contribution of the glutamate and cholinergic mechanisms in the effects of the CCAMs, we conducted experiments with pre-exposure to putative antagonists, NMDA and biperiden. Neither biperiden nor NMDA were able to diminish or cancel the effects of the CCAMs, countering the in vitro data obtained in previous studies. The apparent discrepancy could be related to the specifics of CCAM metabolism or to the interspecies differences between the putative target proteins, possibly due to the relatively low identity percentage of their sequences. Although further research in mammals is required in order to establish their pharmacological properties, novel CCAMs may represent an appealing group of psychoactive drug candidates.
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The effects of ethanol and caffeine exposure on zebrafish, Danio rerio, were investigated using a combination of measurements of behavioral and physiologic responses in a novel tank situation. Ventilation activity as a physiologic measure was measured remotely by monitoring ventilation-related bioelectric signals from freely moving zebrafish in the test tank. The directions of the behavioral responses, except for outer area preference, were substantially the same in both ethanol- and caffeine-treated fish and qualitatively indistinguishable, suggesting that relying solely on behavioral measures may lead to inappropriate interpretation of drug effects when depending on limited behavioral parameters. By incorporating ventilation activity-related physiologic measures into the quantification of drug effects in novel tank tests, more-accurate evaluations of differences in the effects of moderate doses of anxiolytic ethanol and anxiogenic caffeine were possible. Here, we propose that combining physiologic measures such as ventilation rate and its variability with behavioral measures makes it possible to characterize the effects of environmental challenges on zebrafish in a multi-dimensional and more-detailed manner.
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Ansiolíticos , Pez Cebra , Animales , Pez Cebra/fisiología , Cafeína/farmacología , Conducta Animal/fisiología , Ansiolíticos/farmacología , Etanol/farmacología , Ansiedad/tratamiento farmacológicoRESUMEN
Individual differences in exploratory behavior have been found across a range of taxa and are thought to contribute to evolutionary fitness. Animals that explore more of a novel environment and visit areas of high predation risk are considered bold, whereas animals with the opposite behavioral pattern are shy. Here, we determined whether this bimodal characterization of bold versus shy adequately captures the breadth of behavioral variation in zebrafish or if there are more than these two subtypes. To identify behavioral categories, we applied unsupervised machine to three-dimensional swim traces from over 400 adult zebrafish across four strains (AB, TL, TU, and WIK) and both sexes. We found that behavior stratified into four distinct clusters: previously described bold and shy behavior and two new behavioral types we call wall-huggers and active explorers. Clusters were stable across time and influenced by strain and sex where we found that TLs were shy, female TU fish were bold, male TU fish were active explorers, and male ABs were wall-huggers. Our work suggests that zebrafish exploratory behavior has greater complexity than previously recognized and lays the groundwork for the use of zebrafish in understanding the biological basis of individual differences in behavior.
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Conducta Exploratoria , Pez Cebra , Animales , Femenino , Masculino , NataciónRESUMEN
Bioelectric signals related to ventilatory movements in fish can be detected via externally located electrodes. In this study, a technique to continuously monitor the electric ventilatory signals in free-swimming zebrafish was developed. This technique was applied to monitoring ventilation activity as a physiological measure in conjunction with various behavioral measures in a novel tank environment. It was found that in addition to ventilation rate, time domain analysis of changes in ventilation rate is useful for evaluating the emotional state of zebrafish. By integrating the physiological and behavioral measures in analyses, a 1 h novel tank test trial revealed that the habituation process involves two phases. The first phase, which lasted 10 min, involved rapid attenuation of the initial fear/anxiety response to encountering a novel environment. The second phase lasted 20 min and involved further attenuation of anxiety and an increase in exploration behavior. These data suggest that combining ventilation-related physiological measures with conventional behavioral measures enables multidimensional examination of the habituation process in a novel tank environment with more precision than is possible when relying on behavioral responses alone.
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Natación , Pez Cebra , Animales , Ansiedad/psicología , Conducta Animal/fisiología , Conducta Exploratoria , Natación/fisiología , Pez Cebra/fisiologíaRESUMEN
Clitorea ternatea has been used in Ayurvedic medicine as a brain stimulant to treat mental illnesses and mental functional disorders. In this study, the metabolite profiles of crude C. ternatea root extract (CTRE), ethyl acetate (EA), and 50% aqueous methanol (50% MeOH) fractions were investigated using ultrahigh-performance liquid chromatography-diode array detector-tandem mass spectrometry (UHPLC-DAD-MS/MS), while their effect on the stress-like behavior of zebrafish, pharmacologically induced with reserpine, was investigated. A total of 32 compounds were putatively identified, among which, a series of norneolignans, clitorienolactones, and various flavonoids (flavone, flavonol, isoflavone, and isoflavanone) was found to comprise the major constituents, particularly in the EA and 50% MeOH fractions. The clitorienolactones, presently unique to the species, were present in both the free and glycosylated forms in the roots. Both the EA and 50% MeOH fractions displayed moderate effects on the stress-induced zebrafish model, significantly decreasing freezing duration and elevating the total distance travelled and average velocity, 72 h post-treatment. The results of the present study provide further evidence that the basis for the use of C. ternatea roots in traditional medicine to alleviate brain-related conditions, such as stress and depression, is attributable to the presence of clitorienolactones and the isoflavonoidal constituents.
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Clitoria/química , Depresión/tratamiento farmacológico , Flavonoides/farmacología , Lactonas/farmacología , Extractos Vegetales/farmacología , Raíces de Plantas/química , Estrés Fisiológico/efectos de los fármacos , Animales , Conducta Animal , Depresión/inducido químicamente , Isoflavonas/farmacología , Reserpina/toxicidad , Pez CebraRESUMEN
Effects of acute treatment with antidepressant drugs, imipramine and citalopram, on behavior and activity of striatal-enriched tyrosine protein phosphatase (STEP) in the whole brain of zebrafish Danio rerio were studied. Mature zebrafish were exposed for 3 h to water (control) or to solutions of 0.25, 0.5, or 1 mg/liter of imipramine or citalopram, and then their behavior was studied in novel tank test. STEP activity was assayed in the brain of animals by the difference between the rates of transformation of p-nitrophenyl phosphate to 4-nitrophenol in the absence or presence of a selective STEP inhibitor. In novel tank test, imipramine and citalopram reduced locomotor activity and increased freezing time; at this, imipramine increased the total time spent in top of the tank. Citalopram (all concentrations) and imipramine (0.5 and 1 mg/liter) increased STEP activity in zebrafish brain.
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Encéfalo/metabolismo , Citalopram/farmacología , Imipramina/farmacología , Proteínas Tirosina Fosfatasas/metabolismo , Animales , Antidepresivos/farmacología , Encéfalo/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Femenino , Masculino , Pez CebraRESUMEN
Several studies have used zebrafish to investigate the effects of environmental enrichment on behavior and physiology. However, to date there are no studies evaluating the behavioral responses, such as habituation and exploration, of enriched-housed zebrafish when they are submitted to novelty paradigms. The present work was, therefore, designed to evaluate the habituation and exploratory responses of zebrafish exposed to enriched- (EE) and non-enriched (NE) environments when they face novelty. Adult wild-type zebrafish were used. Three different enriched contexts were designed. In Context 1, zebrafish was exposed to enrichment during 7 days, which reduced their total distance traveled in novel tank and social preference tests in comparison to the non-enriched animals. In Context 2, animals were exposed to same enrichment during 14 days. EE exposure did not alter the behavioral responses of zebrafish compared to NE. In Context 3, fish were exposed to enrichment during 14 days, with changing the enriching elements at day 8. Similarly to Context 1, total distance traveled was reduced by EE exposure when compared to NE. Our results suggest a modulatory effect of EE on adult zebrafish locomotion that may be dependent on the time of exposure and on the physical structure of the enriched environment.
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Conducta Animal , Pez Cebra , Animales , Conducta Exploratoria , LocomociónRESUMEN
The use of juvenile and larval fish models has been growing in importance for several fields. Accordingly, the evaluation of behavioural tests that can be applied to larvae and juveniles is becoming increasingly important. We tested medaka at four different ages (1, 10, 30, and 120 dph) in the open field test, one of the most commonly used behavioural assays, to investigate its suitability for larvae and juveniles of this species. We also explored ontogenetic variation in behaviour during this test. On average, adult 120-day-old medaka showed higher locomotor activity in terms of distance moved compared with younger fish. Our analysis suggests that this effect was derived from both quantitative changes in locomotion related to the ontogenetic increase in fish size as well as qualitative changes in two aspects of locomotor behaviour. Specifically, time spent moving was similar between 1- and 10-day-old medaka, but progressively increased with development. In addition, we revealed that adult medaka showed constant levels of activity, whereas younger medaka progressively reduced their activity over the course of the entire experiment. The thigmotaxis behaviour typically used to assess anxiety in the open field test emerged at 120 days post-hatching, even though a difference in the temporal pattern of spatial preference emerged earlier, between 10 and 30 days post-hatching. In conclusion, some measures of the open field test such as total distance moved allow behavioural phenotyping in the medaka of all ages, although with some degree of quantitative and qualitative developmental variation. In contrast, immature medaka appear not to exhibit thigmotactic behaviour.
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Photoaffinity labeling (PAL) remains one of the most widely utilized methods of determining protein targets of drugs. Although useful, the scope of this technique has been limited to in vitro applications because of the inability of UV light to penetrate whole organisms. Herein, pigment-free Casper zebrafish were employed to allow in vivo PAL. A methamphetamine-related phenethylamine PAL probe, designated here as 2, demonstrated dose-dependent effects on behavior similar to methamphetamine and permitted concentration-dependent labeling of protein binding partners. Click chemistry was used to analyze binding partners via fluoroimaging. Conjugation to a biotin permitted streptavidin pull-down and proteomic analysis to define direct binding partners of the methamphetamine probe. Bioinformatic analysis revealed the probe was chiefly bound to proteins involved in phagocytosis and mitochondrial function. Future applications of this experimental paradigm combining examination of drug-protein binding interactions alongside neurobehavioral readouts via in vivo PAL will significantly enhance our understanding of drug targets, mechanism(s) of action, and toxicity/lethality.
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Metanfetamina , Pez Cebra , Animales , Etiquetas de Fotoafinidad , Proteínas , ProteómicaRESUMEN
Zebrafish is becoming a popular animal model in neuropharmacology and drug discovery, mainly due to its ease of handling and low costs involved in maintenance and experimental work. This animal displays a series of complex behaviours that makes it useful for assessing the effects of psychoactive drugs. Here, adult zebrafish were used for assessment of the anxiolytic and anti-addictive properties of UFR2709, a nicotinic receptor (nAChR) antagonist, using two behavioural paradigms to test for addiction, the novel tank diving test to assess anxiety and the conditioned place preference (CPP). Furthermore, the expression of nAChR subunits α4 and α7 was measured in the zebrafish brain. The results show that UFR2709 exhibits an anxiolytic effect on zebrafish and blocks the effect evoked by nicotine on CPP. Moreover, UFR2709 significantly decreased the expression of α4 nicotinic receptor subunit. This indicates that UFR2709 might be a useful drug for the treatment of nicotine addiction.
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Ansiolíticos/farmacología , Ansiedad/prevención & control , Conducta Animal/efectos de los fármacos , Benzoatos/farmacología , Nicotina/antagonistas & inhibidores , Antagonistas Nicotínicos/farmacología , Pirrolidinas/farmacología , Receptores Nicotínicos/metabolismo , Recompensa , Animales , Ansiedad/inducido químicamente , Modelos Animales de Enfermedad , Nicotina/administración & dosificación , Receptores Nicotínicos/genética , Natación , Pez CebraRESUMEN
Zebrafish has become an animal model in research and articles have established ideal conditions for their maintenance. However, little is known regarding the influence of gender and other cues on zebrafish behavior. Thus, here we analyzed the exploratory and social behavior of different sexes (male and female, mixed or segregated) under different housing conditions with various types of stimuli (visual or/and chemical cues and structural environmental enrichment). Segregated females and males were more active than mixed individuals and females were more anxious. Fish that visualized and smelled the opposite sex presented higher activity and were less anxious than individuals that only smelled or visualized the opposite sex. Fish segregated by sex while being allowed to visualize and smell the opposite sex with the presence of structural environmental enrichment exhibited lower activity and anxiety-like behavior than fish without structural environmental enrichment. Thus, we emphasized that these variables should be taken into account in housing conditions and should be detailed for better replicability and reproducibility of experiments performed with zebrafish.
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Conducta Animal , Pez Cebra , Animales , Conducta Exploratoria , Femenino , Vivienda para Animales , Masculino , Reproducibilidad de los Resultados , Conducta SocialRESUMEN
Impairment in glucose regulation is an indicatory effect capable of mediating multiple dysfunction such as cerebrovascular disorder with ischemia and brain damage inclusive. This study aims at investigating the glucose-lowering and neuroprotective capability of Diosgenin (DG) towards hyperglycemia-induced cerebral injury in a developed type 2 diabetes mellitus (T2DM) Zebrafish (ZF) model. T2DM was developed in ZF with 20 mg/kg body weight (b.w) multiple-low dose (MLD) Streptozotocin (STZ) for 28 days. Different doses of 20 mg/kg b.w (DG1) and 40 mg/kg b.w (DG2) DG was intraperitoneally administered twice in 7 days for a period of 28 days after T2DM was completely developed. Weight and behavioral changes were monitored and the catalytic activity including the plasma glucose level of diseased and treated ZF was spectrometrically estimated. Histopathological studies were employed to image the brain pathological condition during disease and treatment. SPSS was used as the statistical tool for result analysis and comparison of data obtained. STZ significantly (###p < 0.001) induced hyperglycemia when compared to control as plasma glucose increases from 101.56 ± 4.52 mgdL-1 to 175.87 ± 6.00 mg/dL. Our results have indicated a marked reduction in glucose concentration from a mean average of 175.87 ± 6.00 mgdL-1 to 105.68 ± 4.48 mgdL-1 and 82.06 ± 7.27 mgdL-1 in DG 1 and DG 2 respectively. Catalytic activity significantly decreases (p < 0.05) from 206.42 ± 30.77 unit/mL to 123.85 ± 29.99 unit/mL at a minimum and maximum value of 103.21 and 275.23 in diseased ZF respectively. On DG treatment, catalytic activity significantly (p < 0.01) rise from 101.58 ± 11.29 and 130.73 ± 27.52 to 130.98 ± 17.13 and 255.96 ± 30.34 with DG1 and DG2 treatment respectively. Studies on the behavioral pattern of STZ-induced anxiolytic effect on ZF confirmed changes in the number of transitions and time spent in both Novel tank test (NTT) and Dark/light test (LDT). Histopathological analysis confirmed the cerebral cortex with inflammatory brain cells in the diseased condition and an attenuation of damage posed revealed in diseased state was largely reversed with DG. As compared to the normal control, a significant ( # p < 0.05 and ### p < 0.001) changes in weight of fishes were recorded and DG1 and DG2 significantly promotes (***p < 0.001) body weight and improves the irregularities in weight of ZF during disease progression. Our study confirms that the potential of DG towards the management of hyperglycemia and hyperglycemia-mediated cerebral ischemic injury is through its blood glucose-lowering properties, anti-inflammatory activity, antioxidant effect, and anxiolytic capabilities.
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Aversive conditions elicit anxiety responses that prepare the organism to an eventual threat. Nonetheless, prolonged anxiety is a pathological condition associated with various neuropsychiatric disorders. Here, we evaluated whether the conspecific alarm substance (CAS), a chemical cue that elicits aversion, influences anxiety-like behaviors and modulates brain oxidative stress-related parameters in wild-type (WT) and leopard (leo) zebrafish following a repeated exposure protocol. CAS exposure was performed for 5â¯min, once daily for 7 consecutive days. In the 8th day, animals were tested in the light/dark and novel tank tests and their brains were further dissected for biochemical analyses. CAS chronically induced anxiogenic-like states in WT and leo populations when their behaviors were analyzed in the light/dark and novel tank tests. CAS also increased catalase (CAT) and glutathione S-transferase (GST) activities, as well as non-protein thiol (NPSH) content in WT and leo, but only leo had increased thiobarbituric reactive substance (TBARS) levels in the brain. At baseline conditions, leo was more 'anxious' when compared to WT, displaying lower CAT activity and carbonylated protein (CP) levels. Overall, CAS chronically triggers anxiety-like behavior in zebrafish populations, which may be associated with changes in oxidative stress-related parameters. Furthermore, the use of different zebrafish populations may serve as an interesting tool in future research aiming to investigate the neurobehavioral bases of neuropsychiatric disorders in vertebrates.
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Ansiedad/fisiopatología , Reacción de Prevención/fisiología , Encéfalo/fisiopatología , Conducta Exploratoria/fisiología , Miedo/fisiología , Reacción Cataléptica de Congelación/fisiología , Estrés Oxidativo , Pez Cebra/fisiología , Animales , Ansiedad/inducido químicamente , Ansiedad/genética , Reacción de Prevención/efectos de los fármacos , Encéfalo/metabolismo , Catalasa/análisis , Conducta Exploratoria/efectos de los fármacos , Miedo/efectos de los fármacos , Femenino , Reacción Cataléptica de Congelación/efectos de los fármacos , Glutatión Transferasa/análisis , Peroxidación de Lípido/efectos de los fármacos , Masculino , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Proteínas Nucleares/fisiología , Estrés Oxidativo/efectos de los fármacos , Feromonas/farmacología , Carbonilación Proteica/efectos de los fármacos , Compuestos de Sulfhidrilo/análisis , Superóxido Dismutasa/análisis , Extractos de Tejidos/farmacología , Pez Cebra/genética , Proteínas de Pez Cebra/análisis , Proteínas de Pez Cebra/deficiencia , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/fisiologíaRESUMEN
Aeromonosis is a fish disease that leads to haemorrhagic septicaemia and high mortality. The detection of early behavioural changes associated to this disease could be helpful in anticipating the initiation of treatment, increasing the probability of success. The influence of this disease on the hypothalamic-pituitary-interrenal (HPI) axis and on the brain expression of heat shock proteins (HSP) is little known. Therefore, the aim of this study was to evaluate the effect of Aeromonas hydrophila infection on individual behaviour and brain expression of genes related to stress (slc6a2, hsp90, hspa12a, hsd20b, hsd11b2, crh) in silver catfish (Rhamdia quelen). Thirty fish were divided into healthy and infected groups. The fish of the infected group were inoculated intramuscularly with 50⯵L of bacterial suspension (6.4â¯×â¯108â¯CFU/mL), while control animals received 50⯵L of saline. On day five post-infection, animals were submitted to the novel tank test, euthanized, and the brain was collected for molecular analysis. Infected fish swam more in the unknown aquarium and presented an increase in brain expression of genes related to HSP (hspa12a) and the route of cortisol synthesis (crh) when compared to uninfected fish. Therefore, this disease causes hyperlocomotion related to stress.
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Aeromonas hydrophila/patogenicidad , Bagres/microbiología , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/fisiopatología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/fisiopatología , Infecciones por Bacterias Gramnegativas/veterinaria , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , Animales , Conducta Animal , Encéfalo/metabolismo , Bagres/genética , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Proteínas HSP90 de Choque Térmico/genética , Proteínas de Choque Térmico/genética , Locomoción , Masculino , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/genéticaRESUMEN
Pharmacological agents acting at alpha-2 adrenergic receptors are widely used in physiology and neuroscience research. Mounting evidence of their potential utility in clinical and experimental psychopharmacology, necessitates new models and novel model organisms for their screening. Here, we characterize behavioral effects of mafedine (6-oxo-1-phenyl-2- (phenylamino)-1,6-dihydropyrimidine-4-sodium olate), a novel drug with alpha-2 adrenergic receptor agonistic effects, in adult zebrafish (Danio rerio) in the novel tank test of anxiety and activity. Following an acute 20-min exposure, mafedine at 60 mg/L produced a mild psychostimulant action with some anxiogenic-like effects. Repeated acute 20-min/day administration of mafedine for 7 consecutive days at 1, 5 and 10 mg/L had a similar action on fish behavior as an acute exposure to 60 mg/L. Since mafedine demonstrated robust behavioral effects in zebrafish - a sensitive vertebrate aquatic model, it is likely that it may modulate rodent and human behavior as well. Thus, further studies are needed to explore this possibility in detail, and whether it may foster clinical application of mafedine and related alpha-2 adrenergic agents.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Conducta Animal/efectos de los fármacos , Mafenida/farmacología , Animales , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Pez CebraRESUMEN
Here we show that the feeding regimen modulates zebrafish (Danio rerio) behavior. With regard to the time elapsed between feeding and behavioral evaluation, fish fed 3 h before behavioral evaluation in the novel tank test (NTT) showed decreased activity and a trend toward an anxiolytic reaction (increased use of the upper section of the aquarium) in comparison to fish fed 0.5, 6, 12, 24 or 48 h before testing, although differences were not statistically significant for all comparisons. Activity and use of the upper section of the aquarium did not differ significantly among the other treatments. Regarding feeding frequency, fish fed once a day showed higher anxiety-like behavior (decreased use of the upper section of the aquarium) in comparison to fish fed twice a day, but feeding four or six times per day or only every second day did not result in differences from feeding twice a day. Feeding frequency had no effect on activity level. Metabolically, fish fed once a day presented decreased levels of glucose and glycogen and increased lactate when compared to the regular feeding (fish fed twice a day), suggesting that feeding regimen may modulate carbohydrate metabolism. Mechanistically, we suggest that the metabolic changes caused by the feeding regimen may induce behavioral changes. Our results suggest that the high variability of the results among different laboratories might be related to different feeding protocols. Therefore, if issues pertaining to the feeding regimen are not considered during experiments with zebrafish, erroneous interpretations of datasets may occur.
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We compared the effect of a new potential antidepressant 8-trifluoromethyl 1,2,3,4,5-benzopentathiepine-6-amine hydrochloride (TC-2153) and classical antidepressant fluoxetine in a dose of 0.25 mg/liter on the behavior of Danio rerio in the "novel tank" test and content of biogenic amines and their metabolites in the brain. Fluoxetine alone and TC-2153 alone significantly increased the time spent in the upper part of the tank and insignificantly reduced motor activity. Combined exposure of fishes in the solution containing potential and classical antidepressants potentiated their effects on both parameters. The compounds did not affect brain contents of serotonin, dopamine, and norepinephrine. At the same time, fluoxetine, but not TC-2153, reduced brain content of the main serotonin metabolite 5-hydroxyindole acetic acid.