Renan Idalencio

Acute exposure to waterborne psychoactive drugs attract zebrafish.

Psychotropic medications are widely used, and their prescription has increased worldwide, consequently increasing their presence in aquatic environments. Therefore, aquatic organisms can be exposed to psychotropic drugs that may be potentially dangerous, raising the question of whether these drugs are attractive or aversive to fish. To answer this question, adult zebrafish were tested in a chamber that allows the fish to escape or seek a lane of contaminated water. These attraction and aversion paradigms were evaluated by exposing the zebrafish to the presence of acute contamination with these compounds. The zebrafish were attracted by certain concentrations of diazepam, fluoxetine, risperidone and buspirone, which were most likely detected by olfaction, because this behavior was absent in anosmic fish. These findings suggest that despite their deleterious effects, certain psychoactive drugs attract fish.

My stress, our stress: blunted cortisol response to stress in isolated housed zebrafish.

Here, we show that individually housed zebrafish presented a reduced cortisol response to an acute stressor (persecution with a pen net for 120 s) compared to zebrafish housed in groups of 10. We hypothesized that the cortisol response to stress was reduced in individually housed zebrafish because they depend solely on their own perceptions of the stressor, whereas among grouped zebrafish, the stress response might be augmented by chemical and/or behavioral cues from the other members of the shoal. This hypothesis was based on previous described chemical communication of stress in fish as well on individual variation in stressor perception and potential individual differences in fish personality.

Waterborne Risperidone Decreases Stress Response in Zebrafish.

The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but its impacts on aquatic organisms are not yet well understood. This study investigated the effects of acute exposure to the antipsychotic risperidone on the stress and behavioral responses in zebrafish. It became clear that intermediate concentration of risperidone inhibited the hypothalamic-pituitary-interrenal axis and displayed anxiolytic-like effects in zebrafish. The data presented here suggest that the presence of this antipsychotic in aquatic environments can alter neuroendocrine and behavior profiles in zebrafish.

Waterborne psychoactive drugs impair the initial development of Zebrafish

The contamination of rivers and other natural water bodies, including underground waters, is a current reality. Human occupation and some economic activities generate a wide range of contaminated effluents that reach these water resources, including psychotropic drug residues. Here we show that fluoxetine, diazepam and risperidone affected the initial development of zebrafish. All drugs increased mortality rate and heart frequency and decreased larvae length. In addition, risperidone and fluoxetine decreased egg hatching. The overall results points to a strong potential of these drugs to cause a negative impact on zebrafish initial development and, since the larvae viability was reduced, promote adverse effects at the population level. We hypothesized that eggs and larvae absorbed the drugs that exert its effects in the central nervous system. These effects on early development may have significant environmental implications.

Waterborne aripiprazole blunts the stress response in zebrafish

Here we provide, at least to our knowledge, the first evidence that aripiprazole (APPZ) in the water blunts the stress response of exposed fish in a concentration ten times lower than the concentration detected in the environment. Although the mechanism of APPZ in the neuroendocrine axis is not yet determined, our results highlight that the presence of APPZ residues in the environment may interfere with the stress responses in fish. Since an adequate stress response is crucial to restore fish homeostasis after stressors, fish with impaired stress response may have trouble to cope with natural and/or imposed stressors with consequences to their welfare and survival.

Stress responses to conspecific visual cues of predation risk in zebrafish

Chemical communication relating to predation risk is a trait common among fish species. Prey fish under threat of predation can signal risk to conspecific fish, which then exhibit defensive responses. Fish also assess predation risk by visual cues and change their behavior accordingly. Here, we explored whether these behavioral changes act as visual alarm signals to conspecific fish that are not initially under risk. We show that shoals of zebrafish (Danio rerio) visually exposed to a predator display antipredator behaviors. In addition, these defensive maneuvers trigger antipredator reactions in conspecifics and, concomitantly, stimulate the hypothalamus-pituitary-interrenal axis, leading to cortisol increase. Thus, we conclude that zebrafish defensive behaviors act as visual alarm cues that induce antipredator and stress response in conspecific fish.

α-Methyltyrosine, a tyrosine hydroxylase inhibitor, decreases stress response in zebrafish (Danio rerio)

In this article, we show that the tyrosine hydroxylase inhibitor α-Methyl-l-tyrosine (AMPT) decreased the responsiveness of the zebrafish stress axis to an acute stressful challenge. These effects were specific for responses to stimulation, since unstimulated (basal) cortisol levels were not altered by AMPT. Moreover, AMPT decreased the stress response 15min after stimulation, but not after that time period. To our knowledge, this is the first report about the effects of AMPT on the neuroendocrine axis of adult zebrafish in acute stress responses. Overall, these results suggest a mechanism of catecholamine-glucocorticoid interplay in neuroendocrine responses of fish, pointing an interesting avenue for physiological research, as well as an important endpoint that can be disrupted by environmental contamination. Further experiments will unravel the mechanisms by which AMPT blocked the cortisol response.

Muscarinic receptors mediate the endocrine-disrupting effects of an organophosphorus insecticide in zebrafish: SANTOS DA ROSA et al.

The glucocorticoid cortisol, the end product of hypothalamus‐pituitary‐interrenal axis in zebrafish (Danio rerio), is synthesized via steroidogenesis and promotes important physiological regulations in response to a stressor. The failure of this axis leads to inability to cope with environmental challenges preventing adaptive processes in order to restore homeostasis. Pesticides and agrichemicals are widely used, and may constitute an important class of environmental pollutants when reach aquatic ecosystems and nontarget species. These chemical compounds may disrupt hypothalamus‐pituitary‐interrenal axis by altering synthesis, structure or function of its constituents. We present evidence that organophosphorus exposure disrupts stress response by altering the expression of key genes of the neural steroidogenesis, causing downregulation of star, hsp70, and pomc genes. This appears to be mediated via muscarinic receptors, since the muscarinic antagonist scopolamine blocked these effects.

Divergent action of fluoxetine in zebrafish according to responsivity to novelty

Here we show that the novel object recognition test can discriminate between high (HRN, neophobic) and low (LRN, neophilic) novelty responders in zebrafish populations. Especially when we observe the latency to the first entry in the novel object zone, zebrafish did not maintain these behavioral phenotypes in sequential tests and only the HRN group returned to their initial responsive behavior when exposed to fluoxetine. Our results have important implications for behavioral data analysis since such behavioral differences can potentially increase individual response variability and interfere with the outcomes obtained from various behavioral tasks. Our data reinforce the validity of personality determination in zebrafish since we show clear differences in behavior in response to fluoxetine.

Feeding regimen modulates zebrafish behavior

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.