Decision-making under stress: A psychological and neurobiological integrative model.

Understanding the impact of stress on cognitive processes, particularly decision-making, is crucial as it underpins behaviors essential for survival. However, research in this domain has yielded disparate results, with inconsistencies evident across stress-induction paradigms and drug administration protocols designed to investigate specific stress pathways or neuromodulators. Building upon empirical studies, this research identifies a multifaceted matrix of variables contributing to the divergent findings. This matrix encompasses factors such as the temporal proximity between stressors and decision tasks, the nature of stressors and decision contexts, individual characteristics including psychobiological profiles and affective states at the time of decision-making and even cultural influences. In response to these complexities, we propose a comprehensive model that integrates these relevant factors and their intricate interplay to elucidate the mechanisms governing decision-making during stressful events. By synthesizing these insights, our model not only refines existing paradigms but also provides a framework for future study designs, offering avenues for theoretical advancements and translational developments in the field of stress's impact on cognitive functions. This research contributes to a deeper understanding of the nuanced relationship between stress and decision-making, ultimately advancing our knowledge of cognitive processes under challenging conditions.

Pharmacological Modulation of Temporal Discounting: A Systematic Review.

Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting.

Structural environmental enrichment and the way it is offered influence cognitive judgement bias and anxiety-like behaviours in zebrafish.

Environmental enrichment in zebrafish generally reduces anxiety-related behaviours, improves learning in maze trials and increases health and biological fitness. However, certain types of enrichment or certain conditions induce the opposite effects. Therefore, it is essential to study the characteristics of environmental enrichment that modulate these effects. This study aims to investigate if structural environmental enrichment and the way it is offered influence cognitive judgement bias and anxiety-like behaviours in adult zebrafish. The fish were assigned to six housing manipulations: constant barren, constant enrichment, gradual gain of enrichment, gradual loss of enrichment, sudden gain of enrichment and sudden loss of enrichment. We then transposed the cognitive judgment bias paradigm, formerly used in studies on other animals to measure the link between emotion and cognition, to objectively assess the impact of these manipulations on the zebrafish's interpretation of ambiguous stimuli, considering previous experiences and related emotional states. We used two battery tests (light/dark and activity tests), which measured anxiety-related behaviours to check if these tests covariate with cognitive bias results. The fish with a sudden gain in enrichment showed a pessimistic bias (interpreted ambiguous stimuli as negative). In addition, the fish that experienced a sudden gain and a gradual loss in enrichment showed more anxiety-like behaviours than the fish that experienced constant conditions or a gradual gain in enrichment. The data provide some proof that structural environmental enrichment and the way it is presented can alter zebrafish's cognitive bias and anxiety-like behaviours.

Putative Activation of Cannabinoid Receptor Type 1 Prevents Brain Oxidative Stress and Inhibits Aggressive-Like Behavior in Zebrafish.

Background: Aggression is a set of complex behaviors commonly described in different neurological disorders, such as schizophrenia, autistim spectrum disorder, and anxiety. Previous studies have described that some changes in the redox status of the brain are closely associated with aggressive behavior in different species. In addition, the endocannabinoid system acts as a neuromodulator of the central nervous system, however, its participation in aggressive behavior needs to be elucidated. Danio rerio (zebrafish) is an important model in the study of aggression, in this context, the present study investigated whether the activation of type 1 cannabinoid receptors (CB1r) alters the cerebral redox state and aggressive behavior in zebrafish. Materials and Methods: We performed pharmacological manipulations with the CB1r agonist (ACEA) and antagonist (AM-251) to assess the role of this receptor in aggressive behavior. Individuals were isolated in pairs, without physical contact for 24 h, treated with the drugs of interest, and after 30 minutes of pharmacokinetics, the fights were filmed for 30 min, and the individuals were identified as dominant or subordinate. Results: A consistent decrease in the strike and bite aggressive behavior was observed in the group treated with the ACEA agonist compared with that in the control and AM-251 groups. When evaluating the cerebral redox state, we observed that treatment with the ACEA agonist reduced malondialdehyde (MDA) levels and increased the levels of sulfhydryl groups compared with those in the control group. These results indicate that the activation of CB1r by the ACEA agonist inhibited aggressiveness and attenuated the levels of oxidative stress in both subjects (dominant or subordinate) in the treated group. Conclusion: Thus, we suggest that zebrafish is an alternative model to study common aggressive behavior disorders among species and that CB1r represent a potential target for the development of treatments for aggressive disorders.

Different influences of anxiety models, environmental enrichment, standard conditions and intraspecies variation (sex, personality and strain) on stress and quality of life in adult and juvenile zebrafish: A systematic review.

Antagonist and long-lasting environmental manipulations (EM) have successfully induced or reduced the stress responses and quality of life of zebrafish. For instance, environmental enrichment (EE) generally reduces anxiety-related behaviours and improves immunity, while unpredictable chronic stress (UCS) and aquarium-related stressors generate the opposite effects. However, there is an absence of consistency in outcomes for some EM, such as acute exposure to stressors, social enrichment and some items of structural enrichment. Therefore, considering intraspecies variation (sex, personality, and strain), increasing intervention complexity while improving standardisation of protocols and contemplating the possibility that EE may act as a mild stressor on a spectrum between too much (UCS) and too little (standard conditions) stress intensity or stimulation, would reduce the inconsistencies of these outcomes. It would also help explore the mechanism behind stress resilience and to standardise EM protocols. Thus, this review critically analyses and compares knowledge existing over the last decade concerning environmental manipulations for zebrafish and the influences that sex, strain, and personality may have on behavioural, physiological, and fitness-related responses.

Putative Activation of the CB1 Cannabinoid Receptors Prevents Anxiety-Like Behavior, Oxidative Stress, and GABA Decrease in the Brain of Zebrafish Submitted to Acute Restraint Stress.

Anxiety disorder is a well-recognized condition observed in subjects submitted to acute stress. Although the brain mechanisms underlying this disorder remain unclear, the available evidence indicates that oxidative stress and GABAergic dysfunction mediate the generation of stress-induced anxiety. Cannabinoids are known to be efficient modulators of behavior, given that the activation of the cannabinoid receptors type-1 (CB1 receptors) induces anxiolytic-like effects in animal models. In the present study, we aimed to describe the effects of the stimulation of the CB1 receptors on anxiety-like behavior, oxidative stress, and the GABA content of the brains of zebrafish submitted to acute restraint stress (ARS). The animals submitted to the ARS protocol presented evident anxiety-like behavior with increased lipid peroxidation in the brain tissue. The evaluation of the levels of GABA in the zebrafish telencephalon presented decreased levels of GABA in the ARS group in comparison with the control. Treatment with ACEA, a specific CB1 receptor agonist, prevented ARS-induced anxiety-like behavior and oxidative stress in the zebrafish brain. ACEA treatment also prevented a decrease in GABA in the telencephalon of the animals submitted to the ARS protocol. Overall, these preclinical data strongly suggest that the CB1 receptors represent a potential target for the development of the treatment of anxiety disorders elicited by acute stress.

Oxidative Stress Mediates Anxiety-Like Behavior Induced by High Caffeine Intake in Zebrafish: Protective Effect of Alpha-Tocopherol.

Anxiety is a common symptom associated with high caffeine intake. Although the neurochemical mechanisms of caffeine-induced anxiety remain unclear, there are some evidences suggesting participation of oxidative stress. Based on these evidences, the current study is aimed at evaluating the possible protective effect of alpha-tocopherol (TPH) against anxiety-like behavior induced by caffeine (CAF) in zebrafish. Adult animals were treated with CAF (100 mg/kg) or TPH (1 mg/kg)+CAF before behavioral and biochemical evaluations. Oxidative stress in the zebrafish brain was evaluated by a lipid peroxidation assay, and anxiety-like behavior was monitored using light/dark preference and novel tank diving test. Caffeine treatment evoked significant elevation of brain MDA levels in the zebrafish brain, and TPH treatment prevented this increase. Caffeine treatment also induced anxiety-like behavior, while this effect was not observed in the TPH+CAF group. Taken together, the current study suggests that TPH treatment is able to inhibit oxidative stress and anxiety-like behavior evoked by caffeine.

White Environment Can Be Used as an Aversive Stimulus in Zebrafish Inhibitory Avoidance Learning.

The two-factor theory predicts that the acquisition of avoidance responses is dependent on fear reduction; as such, drugs that reduce or increase fear or anxiety states should alter inhibitory avoidance (IA) acquisition. The present experiment used white spaces as aversive unconditioned stimuli in IA in zebrafish. Adult zebrafishes were tested in three experiments: validation of white compartment as aversive in IA; open field test; and effect of antidepressant (fluoxetine, imipramine) and anxiolytic (diazepam, clonazepam). The data show the effectiveness of the white compartment as an aversive stimulus in IA. Antidepressant fluoxetine did not alter and imipramine impairs avoidance acquisition in higher doses. Imipramine also produced a sedative effect in lower doses. Anxiolytic and stimulant drugs facilitated learning at doses which did not impair locomotion, suggesting that pharmacological manipulation of other factors in addition to fear/anxiety can impact aversive learning in zebrafish.

Modelagem do comportamento técnico da Luta Marajoara: do desempenho ao educacional / Modeling of the technical behavior of the Marajó Wrestling: from performance to educational

A Luta Marajoara (LM) é uma modalidade esportiva de combate ainda pouco estudada atualmente. Praticada tradicionalmente no Arquipélago do Marajó, Pará, tal modalidade experimenta nos últimos anos um iminente processo de esportivização. O esforço para sua regulamentação enquanto esporte de combate, no entanto, perpassa por aspectos de natureza técnica, de gestão esportiva e de preservação do seu caráter cultural e tradicional. Nesse sentido, vislumbram-se duas possibilidades de intervenções que não são excludentes. Uma que tenta estruturar a LM enquanto modalidade esportiva de combate, e outra que busca sua inserção enquanto conteúdo educacional, no campo da educação física escolar. Perspectivando atrelar valores científicos e educacionais a LM, o presente ensaio tem como objetivo descrever a LM como esta é praticada hoje, identificando suas principais técnicas, aspectos esportivos e características educativas, buscando aplicações tanto no âmbito esportivo quanto no campo educacional. Além das inserções acadêmicas dos autores com outras modalidades esportivas de combate, o estudo pautou-se em levantamento na literatura especializada, em fonte documental de treinadores tradicionais e em conversas com atletas renomados da região do Marajó. Evidencia-se atualmente que a LM vem apresentando um crescente processo de expansão enquanto modalidade de combate, sendo também perceptível, que em termos educacionais, o seu regionalismo e sua dimensão cultural são aspectos que a vinculam cada vez mais com o conteúdo lutas da disciplina educação física escolar. Com este enfoque espera-se que o estudo possa contribuir, enquanto campo de investigação, para o desenvolvimento de uma genuína luta do norte do Brasil, seja em relação ao seu caráter sociocultural e educativo ou a partir de seu dimensionamento enquanto modalidade esportiva de combate....(AU)

The Marajó wrestling (MW) is a combat sports modality still little studied at present. Traditionally practiced in the Archipelago of Marajó, Pará, this modality has experienced in the last years an imminent process of sportification. The effort to regulate it as a combat sport, however, runs through aspects of a technical nature, sports management and preservation of its cultural and traditional character. In this sense, we can see two possibilities for interventions that are not exclusive. One that tries to structure the LM as a sporting combat modality, and another that seeks its insertion as an educational content, in the field of school physical education. Aiming to connect scientific and educational values to LM, this essay aims to describe LM as it is practiced today, identifying its main techniques, sports aspects and educational characteristics, seeking applications both in the sports field and in the educational field. Besides the academic insertions of the authors with other sports modalities of combat, the study was based on a survey in the specialized literature, documentary source of traditional coaches and in conversations with renowned athletes of the Marajó region. It is now evidenced that LM has been presenting a growing process of expansion as a combat modality, and it is also perceptible that, in educational terms, its regionalism and its cultural dimension are aspects that increasingly link it with the content of the education discipline school physics. With this approach it is hoped that the study may contribute, as a field of research, to the development of a genuine struggle of the north of Brazil, be it in relation to its sociocultural and educational character or from its dimensioning as a sporting mode of combat....(AU)

Corrigendum to "Erotic suboptimal stimuli affects moral, decision-making. A cross-cultural comparison" [IBRO Rep. 6S (2019) S66].

[This corrects the article DOI: 10.1016/j.ibror.2019.07.216.].

Mauritia flexuosa L. protects against deficits in memory acquisition and oxidative stress in rat hippocampus induced by methylmercury exposure.

OBJECTIVE: Methylmercury (MeHg) is the most toxic form of mercury that can affect humans through the food chain by bioaccumulation. Human organism is capable of triggering visual and cognitive disorders, neurodegeneration, as well as increased production of reactive species of O2 and depletion of natural anti-oxidant agents. In this context, Mauritia flexuosa L., a fruit rich in compounds with anti-oxidant properties, emerged as an important strategy to prevent the MeHg damages. So, this work has aimed to elucidate the protective effect of Mauritia flexuosa L. on the damage caused by the exposure of rats to MeHg. METHODS: In order to evaluate the effect of MeHg on rat aversive memory acquisition and panic-like behavior, we have used elevated T-maze apparatus and after behavioral test, the hippocampus was removed to perfom lipid peroxidation. RESULTS: Our results demonstrated that the exposure to MeHg caused deficits in inhibitory avoidance acquisition (aversive conditioning) and in the learning process, and increased levels of lipid peroxidation in hippocampus tissue. However, the pretreatment with feed enriched with Mauritia flexuosa L. showed a protective effect against cognitive deficits caused by MeHg and also prevented the occurrence of cytoplasmic membrane damage induced by lipid peroxidation in the hippocampal region. DISCUSSION: Therefore, this study suggests that Mauritia flexuosa L. represents an important strategy to prevent neurocytotoxics and behavioral effects of MeHg.

Reprint of "Pharmacological study of the light/dark preference test in zebrafish (Danio rerio): Waterborne administration".

Anxiety is a complex disorder; thus, its mechanisms remain unclear. Zebrafish (Danio rerio) are a promising pharmacological model for anxiety research. Light/dark preference test is a behaviorally validated measure of anxiety in zebrafish; however, it requires pharmacological validation. We sought to evaluate the sensitivity of the light/dark preference test in adult zebrafish by immersing them in drug solutions containing clonazepam, buspirone, imipramine, fluoxetine, paroxetine, haloperidol, risperidone, propranolol, or ethanol. The time spent in the dark environment, the latency time to first crossing, and the number of midline crossings were analyzed. Intermediate concentrations of clonazepam administered for 600s decreased the time spent in the dark and increased locomotor activity. Buspirone reduced motor activity. Imipramine and fluoxetine increased time spent in the dark and the first latency, and decreased the number of alternations. Paroxetine did not alter the time in the dark; however, it increased the first latency time and decreased locomotor activity. Haloperidol decreased the time spent in the dark at low concentrations. Risperidone and propranolol did not change any parameters. Ethanol reduced the time spent in the dark and increased the number of crossings at intermediate concentrations. These results corroborate the previous work using intraperitoneal drug administration in zebrafish and rodents, suggesting that water drug delivery in zebrafish can effectively be used as an animal anxiety model.

Pharmacological study of the light/dark preference test in zebrafish (Danio rerio): Waterborne administration.

Anxiety is a complex disorder; thus, its mechanisms remain unclear. Zebrafish (Danio rerio) are a promising pharmacological model for anxiety research. Light/dark preference test is a behaviorally validated measure of anxiety in zebrafish; however, it requires pharmacological validation. We sought to evaluate the sensitivity of the light/dark preference test in adult zebrafish by immersing them in drug solutions containing clonazepam, buspirone, imipramine, fluoxetine, paroxetine, haloperidol, risperidone, propranolol, or ethanol. The time spent in the dark environment, the latency time to first crossing, and the number of midline crossings were analyzed. Intermediate concentrations of clonazepam administered for 600s decreased the time spent in the dark and increased locomotor activity. Buspirone reduced motor activity. Imipramine and fluoxetine increased time spent in the dark and the first latency, and decreased the number of alternations. Paroxetine did not alter the time in the dark; however, it increased the first latency time and decreased locomotor activity. Haloperidol decreased the time spent in the dark at low concentrations. Risperidone and propranolol did not change any parameters. Ethanol reduced the time spent in the dark and increased the number of crossings at intermediate concentrations. These results corroborate the previous work using intraperitoneal drug administration in zebrafish and rodents, suggesting that water drug delivery in zebrafish can effectively be used as an animal anxiety model.

Effects of the number of subjects on the dark/light preference of Zebrafish (Danio rerio).

This research aims to describe the effects of a variable number of Danio rerio fish subjects, ranging from one to eight, in the light/dark box preference test. Four hundred eighty adult male short-finned phenotype zebrafish were tested in the light/dark box. There were four groups in this experiment and a different number of subjects was used in each group: the control group had only one subject, whereas the experimental groups had either two, four, or eight subjects simultaneously inside the apparatus in every session. The average occurrence (AO) of subjects in the white side of the aquarium and the first choice average (FC) were recorded. The AO revealed no difference between the control group and test groups with two and four subjects. The results for the test group with eight subjects showed significant difference when compared to the control group and from the test group with two subjects. The FC also showed no difference between the control group and test groups with two and four subjects. There was significant variation between the control and the test group with eight subjects. The results reflect a conflict between the animal's preference for dark places and the innate drive to explore new environments. Zebrafish are highly social animals, exhibiting preference for swimming in groups and other patterns of social cohesion. The reduced white avoidance behavior in the test group of eight subjects may possibly reflect the role of shoaling, which is a defensive behavior, in reducing anxiety and stress. On the other hand, the absence of difference between the control group and test groups with two and four subjects suggest that it is feasible to run the light/dark test with up to four subjects, becoming an alternative to streamline and simplify data collection and test analysis.

Fingerprinting of psychoactive drugs in zebrafish anxiety-like behaviors.

A major hindrance for the development of psychiatric drugs is the prediction of how treatments can alter complex behaviors in assays which have good throughput and physiological complexity. Here we report the development of a medium-throughput screen for drugs which alter anxiety-like behavior in adult zebrafish. The observed phenotypes were clustered according to shared behavioral effects. This barcoding procedure revealed conserved functions of anxiolytic, anxiogenic and psychomotor stimulating drugs and predicted effects of poorly characterized compounds on anxiety. Moreover, anxiolytic drugs all decreased, while anxiogenic drugs increased, serotonin turnover. These results underscore the power of behavioral profiling in adult zebrafish as an approach which combines throughput and physiological complexity in the pharmacological dissection of complex behaviors.

Ascorbic acid protects against anxiogenic-like effect induced by methylmercury in zebrafish: action on the serotonergic system.

To evaluate the protector effect of ascorbic acid (AA) against anxiogenic-like effect induced by methylmercury (MeHg) exposure, adult zebrafish were treated with AA (2 mg g(-1), intraperitoneal [i.p.]) before MeHg administration (1.0 µg g(-1), i.p.). Groups were tested for the light/dark preference as a behavioral model of anxiety, and the content of serotonin and its oxidized metabolite tryptamine-4,5-dione (T-4,5-D) in the brain was determined by high-performance liquid chromatography. MeHg has produced a marked anxiogenic profile in both tests, and this effect was accompanied by a decrease in the extracellular levels of serotonin, and an increase in the extracellular levels of T-4,5-D. Added to this, a marked increase in the formation of a marker of oxidative stress accompanied these parameters. Interestingly, the anxiogenic-like effect and biochemical alterations induced by MeHg were blocked by pretreatment with AA. These results for the first time demonstrated the potential protector action of AA in neurobehavioral and neurochemical alterations induced by methylmecury exposure demonstrating that zebrafish model could be used as an important tool for testing substances with neuroprotector actions.

Minocycline treatment and bone marrow mononuclear cell transplantation after endothelin-1 induced striatal ischemia.

We explored whether the modulation of microglia activation with minocycline is beneficial to the therapeutic actions of bone marrow mononuclear cells (BMMCs) transplanted after experimental stroke. Male Wistar adult rats were divided in four experimental groups: ischemic control saline treated (G1, N = 6), ischemic minocycline treated (G2, N = 5), ischemic BMMC treated (G3, N = 5), and ischemic minocycline/BMMC treated (G4, N = 6). There was a significant reduction in the number of ED1+ cells in G3 animals (51.31 ± 2.41, P < 0.05), but this effect was more prominent following concomitant treatment with minocycline (G4 = 29.78 ± 1.56). There was conspicuous neuronal preservation in the brains of G4 animals (87.97 ± 4.27) compared with control group (G1 = 47.61 ± 2.25, P < 0.05). The behavioral tests showed better functional recovery in animals of G2, G3, and G4, compared with G1 and baseline (P < 0.05). The results suggest that a proper modulation of microglia activity may contribute to a more permissive ischemic environment contributing to increased neuroprotection and functional recovery following striatal ischemia.

Modulation of microglial activation enhances neuroprotection and functional recovery derived from bone marrow mononuclear cell transplantation after cortical ischemia.

Activated microglia may exacerbate damage in neural disorders; however, it is unknown how they affect stem cells transplanted after stroke. Focal ischemia was induced by microinjections of 40 pmol of endothelin-1 into the motor cortex of adult rats. Ischemic animals were treated with sterile saline (n = 5), bone marrow mononuclear cells (BMMCs, n = 8), minocycline (n = 5) or concomitantly with minocycline and BMMCs (n = 5). BMMC-treated animals received 5 × 10(6)BMMCs through the caudal vein 24h post-ischemia. Behavioral tests were performed to evaluate functional recovery. Morphometric and histological analyses were performed to assess infarct area, neuronal loss and microglia/macrophage activation up to 21 days post-ischemia. Treatments with minocycline, BMMCs or minocycline-BMMCs reduced infarct area, increased neuronal survival and decreased the number of caspase-3+ and ED-1+ cells, but these effects were more prominent in the minocycline-BMMC group. Behavioral analyses using the modified sticky-tape and open-field tests showed that ischemic rats concomitantly treated with BMMCs and minocycline showed better motor performance than rats treated with BMMCs or minocycline only. The results suggest that proper modulation of the inflammatory response through the blockage of microglia activation enhances neuroprotection and functional recovery induced by intravenous transplantation of BMMCs after motor cortex ischemia.

Possible role of serotoninergic system in the neurobehavioral impairment induced by acute methylmercury exposure in zebrafish (Danio rerio).

Adult zebrafish were treated acutely with methylmercury (1.0 or 5.0 µg g(-1), i.p.) and, 24h after treatment, were tested in two behavioral models of anxiety, the novel tank and the light/dark preference tests. At the smaller dose, methylmercury produced a marked anxiogenic profile in both tests, while the greater dose produced hyperlocomotion in the novel tank test. These effects were accompanied by a decrease in extracellular levels of serotonin, and an increase in extracellular levels of tryptamine-4,5-dione, a partially oxidized metabolite of serotonin. A marked increase in the formation of malondialdehyde, a marker of oxidative stress, accompanied these parameters. It is suggested that methylmercury-induced oxidative stress produced mitochondrial dysfunction and originated tryptamine-4,5-dione, which could have further inhibited tryptophan hydroxylase. These results underscore the importance of assessing acute, low-level neurobehavioral effects of methylmercury.

Pharmacological analysis of zebrafish (Danio rerio) scototaxis.

The scototaxis test has been introduced recently to assess anxiety-like phenotypes in fish, including zebrafish. Parametric analyses suggest that scototaxis represents an approach-avoidance conflict, which hints at anxiety. In this model, white avoidance represents anxiety-like behavior, while the number of shuttling events represents activity. Acute or chronic fluoxetine, buspirone, benzodiazepines, ethanol, caffeine and dizocilpine were assessed using the light-dark box (scototaxis) test in zebrafish. Acute fluoxetine treatment did not alter white avoidance, but altered locomotion in the higher dose; chronic treatment (2 weeks), on the other hand, produced an anxiolytic effect with no locomotor outcomes. The benzodiazepines produced a hormetic (inverted U-shaped) dose-response profile, with intermediate doses producing anxiolysis and no effect at higher doses; clonazepam, a high-potency benzodiazepine agonist, produced a locomotor impairment at the highest dose. Buspirone produced an anxiolytic profile, without locomotor impairments. Moclobemide did not produce behavioral effects. Ethanol also produced a hormetic profile in white avoidance, with locomotor activation in 0.5% concentration. Caffeine produced an anxiogenic profile, without locomotor effects. These results suggest that the light-dark box is sensitive to anxiolytic and anxiogenic drugs in zebrafish.