Advertisement
Research Article
Environmental enrichment modulates the response to chronic stress in zebrafish
Matheus Marcon, Ricieri Mocelin, Radharani Benvenutti, Tales Costa, Ana P. Herrmann, Diogo L. de Oliveira, Gessi Koakoski, Leonardo J. G. Barcellos, Angelo Piato
Journal of Experimental Biology 2018 221: jeb176735 doi: 10.1242/jeb.176735 Published 22 February 2018

ABSTRACT

Several studies have shown that manipulations to the housing environment modulate susceptibility to stress in laboratory animals, mainly in rodents. Environmental enrichment (EE) is one such manipulation that promotes neuroprotection and neurogenesis, besides affecting behaviors such as drug self-administration. Zebrafish are a popular and useful animal model for behavioral neuroscience studies; however, studies evaluating the impact of housing conditions in this species are scarce. In this study, we verified the effects of EE on behavioral (novel tank test) and biochemical [cortisol and reactive oxygen species (ROS)] parameters in zebrafish submitted to unpredictable chronic stress (UCS). Consistent with our previous findings, UCS increased anxiety-like behavior, cortisol and ROS levels in zebrafish. EE for 21 or 28 days attenuated the effects induced by UCS on behavior and cortisol, and prevented the effects on ROS levels. Our findings reinforce the idea that EE exerts neuromodulatory effects across species, reducing vulnerability to stress and its biochemical impact. Also, these results indicate that zebrafish is a suitable model animal to study the behavioral effects and neurobiological mechanisms related to EE.

INTRODUCTION

Recently, much effort has been made to clarify the effects of environmental enrichment (EE) and to investigate which mechanisms are involved (Young et al., 1999; Rampon et al., 2000; van Praag et al., 2000; Lazarov et al., 2005; Artola et al., 2006; Nithianantharajah and Hannan, 2006; Pang and Hannan, 2013). EE consists of interventions in the housing environment that contribute to improving the welfare of laboratory animals and attempts to resemble their family environment. It provides animals with greater social interaction and exposure to sensory stimuli (visual, motor, cognitive and somatosensory), stimulating several brain regions (Nithianantharajah and Hannan, 2006; Crofton et al., 2015). EE promotes neuroprotection and neurogenesis, and affects behaviors such as drug self-administration and response to stress (Bardo et al., 2001; Green et al., 2003, 2010; Chauvet et al., 2009; El Rawas et al., 2009; Solinas et al., 2009; Stairs and Bardo, 2009).

Evidence suggests that EE has neuromodulatory effects in brain reward circuits, mainly in the mesolimbic dopamine system (Bezard et al., 2003; Zhu et al., 2005; Solinas et al., 2008). Several studies in rodents demonstrated that EE improves hippocampus cytoskeleton, cell proliferation, survival of newborn cells, and increases the number and proportion of post-mitotic immature neurons and dendritic arborization (Bennett et al., 1964; Diamond et al., 1964; Tanti et al., 2013), along with increasing cell viability and glucocorticoid receptor expression (Veena et al., 2009; Sampedro-Piquero et al., 2014). EE promotes important changes in the expression of genes related to synaptic plasticity, neuronal signalling, learning and memory (Rampon et al., 2000). A recent study confirmed that EE induces neuroplasticity in the hippocampus and protection against the effects of unpredictable chronic stress (UCS) in mice (Vega-Rivera et al., 2016).

Regarding behavioral effects, some studies in rats submitted to chronic stress have shown that EE improved working memory performance in the T-maze task, and prevented anxiety-like behavior in the elevated plus maze test (Bhagya et al., 2017). EE also prevented depression-like behavior in the sucrose preference test, and partially prevented the anxiogenic-like effect of chronic stress, attenuating the spatial learning difficulty and memory impairment in the radial arm maze in rodents (Shilpa et al., 2017). Interestingly, zebrafish have been shown to prefer EE even when they are reared in barren conditions (Schroeder et al., 2014). In addition, studies with zebrafish revealed that the EE increased brain size (DePasquale et al., 2016) and proliferation of telencephalic cells (von Krogh et al., 2010), decreased anxiety-like behavior and increased exploration (Manuel et al., 2015), as well as blunting the cortisol response to acute stress in both isolated and group-housed zebrafish (Giacomini et al., 2016).

In addition, studies have demonstrated the involvement of EE with changes in oxidative status. EE prevented the increase in reactive oxygen species (ROS) levels, thiobarbituric acid reactive substances (TBARS) and the superoxide dismutase (SOD) activity induced by chronic cerebral hypoperfusion in rats (Cechetti et al., 2012). Another study that investigated free radical levels through 8-hydroxy-2-deoxyguanosine (8-OH-dG), a marker of oxidative stress associated with DNA, reported that EE attenuated the upregulation induced by inescapable foot shocks in the hippocampus and prefrontal cortex of rats (Sun et al., 2016). Zebrafish exposure to chronic stress alters behavior and increases cortisol levels. Cortisol mobilizes energy reserves to deal with stressors (Kirschbaum et al., 1993), thus increasing mitochondrial respiration and the production of ROS as a by-product (Gutierrez et al., 2006).

Finally, despite the knowledge regarding the effects of EE in rodents, there are no studies investigating if EE could improve chronic stress-related phenomena in zebrafish. Therefore, considering the effects of EE as a neuromodulatory intervention, we hypothesized that EE-housed zebrafish would be less vulnerable to the effects of UCS. This study verified the effects of EE in zebrafish submitted to UCS on behavioral (novel tank test) and biochemical (trunk cortisol and ROS levels) parameters.

MATERIALS AND METHODS

Animals

A total of 96 adult zebrafish, Danio rerio (F. Hamilton 1822), wild-type short fin strain (6 months old, 3–4 cm long; 50:50 male:female ratio) were purchased from Delphis aquariums (Porto Alegre, Brazil). The fish were kept for 15 days in a closed 16 liter acclimation tank system (40×20×24 cm) identical to the experimental tanks (standard condition), with non-chlorinated tap water, well-aerated and a light:dark cycle of 14 h:10 h (lights on at 06:00 h). The tank water was kept at appropriate conditions (pH 7.0±0.3; temperature 26±1°C; total ammonia <0.01 mg l−1; nitrite <0.01 mg l−1; dissolved oxygen 7.0±0.4 mg l−1; alkalinity 22 mg l−1 CaCO3 and total hardness 5.8 mg l−1). The fish were fed twice a day with a commercial flake fish food (Alcon Basic, Alcon, Brazil) and the amount of food was calculated based on the number of fish per tank and followed the manufacturer’s instructions as well as zebrafish literature (4% of body weight in food per fish per day). All experiments were approved by the Ethics Committee of Universidade Federal do Rio Grande do Sul (reference number 30992/2015).

Reagents

2′,7′-Dichlorodihydrofluorescein-diacetate (H2DCF-DA) and phosphate-buffered saline powder (PBS; pH 7.4) were purchased from Sigma-Aldrich (São Paulo, Brazil), and ethyl alcohol (absolute ethanol) from Merck (Brazil). H2DCF-DA was dissolved in 1 mmol l−1 absolute ethanol and maintained at 4°C. A sachet of powdered PBS was diluted in 1 liter of Milli-Q water and maintained at 4°C, pH 7.4.

Housing conditions

After 15 days of acclimation, fish were randomly assigned to an experimental housing condition: standard condition (ST) or environmental enrichment (EE). The ST housing condition consisted only of a tank with water, heater, filter and aeration system (Fig. 1A). The EE housing condition consisted of a tank with gravel in the bottom (English sea stones, 4–9 mm, 3 cm high from the bottom of the tank), a ruin-like plastic object, and three submerged plastic plants (two 10 cm tall and one 20 cm tall), besides all equipment of the standard housing condition (Fig. 1B). Both types of tank were the same size (16-liter volume; 40×20×24 cm), and a piece of white frosted cardboard (30×60 cm) was placed between the tanks to prevent visual contact of fish from different tanks in the same horizontal plane. Tanks were not covered at the front. For every experimental group there were two identical tanks that were kept in the same room, and all the tanks were run in parallel. To confirm that the variation derived from the individual rather than from the tank, we tested for tank effects by including ‘tank’ as a factor in our initial statistical analysis. As we observed no main effects or interactions for the factor ‘tank’ in the ANOVAs, we excluded it as a variable in further analyses, and data from tanks of the same experimental group were pooled together.

Fig. 1.
Fig. 1.

Housing conditions for zebrafish (Danio rerio). (A) Standard condition (ST); (B) environmental enrichment (EE).

Experimental design

The experimental design is shown in Fig. 2. The animals were kept under standard conditions (ST) or environmental enrichment for 21 days (EE21) or 28 days (EE28). In the last 7 days, animals were divided into two sub-cohorts (non-stressed or stressed, respectively: S− and S+). For S+ groups, 24 h after the last stressor animals were individually submitted to the behavioral test and immediately after that were anesthetized by rapid cooling (immersion in water at 2–4°C until unable to swim and cessation of opercular movement). After cessation of opercular movements for 2 min, zebrafish were removed and decapitated. The bodies and head were flash-frozen for whole-body (trunk) cortisol measurement and brain ROS analyses. S– groups were subjected to the same procedures on the 29th day of the experimental protocol.

Fig. 2.
Fig. 2.

Experimental design. The fish were exposed to environmental enrichment (EE) for 21 or 28 days or remained unchanged (standard condition). In the last 7 days of the experimental protocol, they were submitted to the unpredictable chronic stress (UCS) protocol or remained unchanged (control). The day after the last stressor, between 08:00 and 11:00 h, the fish were submitted to the novel tank test and euthanized for biochemical analysis (brain and trunk for the dosage of ROS levels and cortisol, respectively).

Unpredictable chronic stress protocol

The UCS protocol followed our previous studies with slight adaptations (Piato et al., 2011; Marcon et al., 2016; Rambo et al., 2017). In this study, we replaced the social isolation stressor by the stress of exposure to a predator fish (Archocentrus nigrofasciatus). Stressors were presented randomly twice a day to ensure unpredictability and to avoid habituation over 7 days (Table 1). The stressors used were: (i) heating tank water up to 33°C (30 min); (ii) exposure to the predator (50 min); (iii) cooling tank water to 23°C (30 min); (iv) crowding of 12 animals in a 300 ml beaker (50 min); (v) transferring the animals to another tank with low water level, exposing the dorsal body wall (2 min); (vi) tank change, three consecutive times at 30 min intervals; and (vii) chasing with a net (8 min). The non-stressed (S–) animals were left undisturbed throughout the experiments.

View this table:
Table 1.

The procedure of the unpredictable chronic stress protocol

Novel tank test

Twenty-four hours after UCS, the animals were individually submitted to the novel tank test: fish were placed for 6 min in 24×8×20 cm tanks with 15 cm water level. The water in the test apparatus was changed for each group and maintained at 26±1°C. The tanks were virtually divided into three equal horizontal sections (bottom, middle and upper zones). Behavioral tests were video recorded and analyzed with the ANY-Maze tracking software (Stoelting Co., Wood Dale, IL, USA). The following parameters were quantified: total distance traveled, time spent in the bottom and upper zones, and number of transitions to the upper zone (Marcon et al., 2016). Total distance moved was used as an indicator of overall locomotor activity. The time in the bottom zone is used as an indicator of anxiety, while time spent and entries in the upper zone are frequently used to illustrate the effects of anxiolytic interventions. After conducting the behavioral tests, video files were coded and the researcher responsible for behavioral analysis was unaware of the experimental group each animal belonged to.

Cortisol measurement

The extraction and quantification of trunk cortisol were carried out using a commercially available enzyme-linked immunosorbent assay kit (EIAgen Cortisol test, BioChem ImmunoSystems) based on our previous study (Marcon et al., 2016). Briefly, the zebrafish were euthanized and a pool of two zebrafish trunks was minced and 500 mg placed into a disposable stomacher bag with 2 ml of PBS (pH 7.4) for 6 min. Ethyl ether was added and samples were homogenated in a vortex and centrifuged for 10 min at 1000 g. Immediately after centrifugation, samples were frozen in liquid nitrogen. The unfrozen portion (ethyl ether containing cortisol) was decanted and the ethyl ether was transferred to a new tube and completely evaporated under a gentle stream of nitrogen for 2 h, yielding a lipid extract containing the cortisol. The extract was stored at −20°C until the ELISA was conducted on the samples suspended with 1 ml of PBS buffer.

ROS levels

Immediately after the behavioral evaluation, the fish brain was removed and gently homogenized in 150 µl of PBS. The samples were centrifuged at 10,000 g for 10 min at 4°C. The resulting pellets were discarded and the supernatants collected for the dosage of ROS levels. The fluorescent probe H2DCF-DA was used to evaluate the free radical content (LeBel et al., 1990; Ali et al., 1992). A sample aliquot of 25 µl was incubated with 5 µl of 1 mmol l−1 H2DCF-DA and 170 µl of PBS at 37°C for 30 min. ROS levels were detected with a fluorescence microplate reader at emission (520 nm) and excitation (480 nm) wavelengths using dichlorofluorescein (DCF) as standard. Results were expressed as relative fluorescence unit (RFU).

Statistical analysis

The normal distribution of the data and homogeneity of variance was confirmed by Kolmogorov–Smirnov and Levene tests, respectively. Results were analyzed by two-way ANOVA (stress and environmental enrichment as independent factors) followed by Tukey’s post hoc test for comparisons within groups and between housing conditions. Correlation analysis between the time spent in the bottom of the tank and cortisol levels was assessed using Pearson's correlation analysis (we used the mean value from two fish to match the respective cortisol measure from the pooled animals). We conducted three-way ANOVAs with gender as the third independent variable; as no main effects or interactions were observed for gender, data from males and females were pooled together. Differences were considered significant at P<0.05. The data were expressed as means±s.e.m.

RESULTS

Fig. 3 shows the effects of EE on behavioral parameters in zebrafish submitted to UCS. The UCS protocol did not alter total distance traveled (Fig. 3A), but increased the time in the bottom zone, and decreased the time spent and the number of entries to the upper zone of the tank (Fig. 3B–D, respectively). EE did not induce general locomotor alterations as indicated by total distance (Fig. 3A). Although in non-stressed animals EE decreased time and entries to the upper zone, it attenuated the anxiogenic effect of UCS (Fig. 3B,C).

Fig. 3.
Fig. 3.

Effects of environmental enrichment for 21 or 28 days on behavioral parameters (novel tank test) in zebrafish submitted to UCS or not. EE21, environmental enrichment for 21 days; EE28, environmental enrichment for 28 days; ST, standard condition; S+, subjected to UCS; S–, not subjected to UCS. Data are expressed as means±s.e.m.; N=9–12; two-way ANOVA/Tukey’s post hoc test.

Fig. 4 shows the effects of EE on trunk cortisol in zebrafish submitted to UCS. As expected, the UCS protocol increased cortisol levels in animals housed in standard conditions. EE for 21 or 28 days attenuated this response. We also observed a positive correlation between cortisol levels and time spent in the bottom zone of the tank (r=0.4715, P=0.0056), showing the higher the cortisol levels, the more time fish spent in the bottom of the tank.

Fig. 4.
Fig. 4.

Effects of environmental enrichment for 21 or 28 days on cortisol levels in zebrafish submitted to unpredictable chronic stress or not. EE21, environmental enrichment for 21 days; EE28, environmental enrichment for 28 days; ST, standard condition; S+, subjected to UCS; S–, not subjected to UCS. Data are expressed as means±s.e.m.; N =5–6; two-way ANOVA/Tukey’s post hoc test.

Fig. 5 shows the effects of EE on ROS levels in zebrafish submitted to UCS. The UCS protocol increased ROS levels but EE prevented this effect. There was no difference among non-stressed animals (ST×EE21×EE28).

Fig. 5.
Fig. 5.

Effects of environmental enrichment for 21 or 28 days on reactive oxygen species levels in zebrafish submitted to unpredictable chronic stress or not. EE21, environmental enrichment for 21 days; EE28, environmental enrichment for 28 days; ST, standard condition; S+, subjected to UCS; S–, not subjected to UCS. DCF, dichlorofluorescein (relative fluorescence units, RFU). Data are expressed as a means±s.e.m.; N =6–10; two-way ANOVA/Tukey’s post hoc test.

DISCUSSION

Consistent with our previous findings, we show that UCS increased anxiety-like behavior and increased cortisol levels in zebrafish (Piato et al., 2011; Marcon et al., 2016). In this study, we characterize the effects of EE on behavior and biochemical parameter changes induced by UCS. We show that EE for 21 or 28 days attenuated the effects induced by UCS on some behavioral parameters and trunk cortisol, whereas it prevented the effects of UCS on ROS levels.

UCS decreased the time and entries in the upper zone, and EE attenuated these anxiogenic behaviors. Interestingly, non-stressed animals kept in EE conditions seem more anxious in the novel tank test compared with non-stressed animals kept in ST conditions. We hypothesize that the transition from an enriched environment to the novel tank test, which is a barren tank akin to a standard housing condition, represents a novelty factor not present to ST-housed zebrafish, and is thus anxiogenic. Therefore, EE exerts differential effects depending on the stress status of the animals, i.e. is anxiogenic for non-stressed animals and anxiolytic for stressed animals in the novel tank test. This is in agreement with previous studies showing that group-housed zebrafish exhibit higher anxiety-related behavior in the novel tank test when compared with single-housed zebrafish (Parker et al., 2012; Shams et al., 2015). In this context, for fish already acclimated to the conditions of the test (barren tank, single individual) the novel environment will induce less anxiety behavior. It is important to note, however, that we accessed anxiety levels after removing the fish from their housing tanks. Therefore, no inferences can be made regarding the status of the animals while inside their maintenance tanks.

International guidelines recommend EE for animal maintenance and welfare. The feasibility of implementing EE in a zebrafish facility is certainly an important aspect to be considered. Furthermore, few studies have been carried out to address the behavioral consequences of modifying the conditions in which zebrafish are habitually kept in research facilities worldwide. The intention of our investigation was not to suggest the indispensable use of EE to avoid stress in all studies using zebrafish, but rather to elucidate how EE influences zebrafish behavior and biochemical parameters and whether it modifies the response of this species to stress. Our results show that studies previously published in the literature could have reached different conclusions (especially regarding behavior and stress response) if the housing conditions were enriched compared with what they usually are. Future studies in the field are necessary to further advance the discussion.

Rodent studies have reported anxiogenic effects of EE in the sucrose neophobia test, cold-stress defecation (Green et al., 2010) and latency to ejaculation (Urakawa et al., 2014). Alternatively, another study assessed anxiety-related behavior in zebrafish raised in EE and observed decreased anxiety as indicated by increased time spent in the light compartment in the light/dark test (Manuel et al., 2015). This divergence of EE-induced behavior in anxiety tests (novel tank versus light/dark test) suggests that they are measuring distinct, although related, phenomena (Kysil et al., 2017). Furthermore, the differences in the EE protocols may underlie the contrasting observations of animal behavior. Aspects such as the degree of enrichment, types of objects used, length of exposure, reorganization or not of the environment, housing density and age are the main variables (Crofton et al., 2015).

Chronic stress is characterized by sustained activation of the neuroendocrine axis and production of cortisol (Egeland et al., 2015; McEwen et al., 2015). As demonstrated in rodents (Miklós and Kovács, 2012) and recently in zebrafish (Song et al., 2017), chronic stress reshapes the neural networks that regulate neuroendocrine function, providing an anatomical reorganization that renders cortisol responses more sensitive to stress. The sustained release of cortisol leads to mobilization of energy resources and accelerates cellular metabolic processes (Otte et al., 2016), increasing oxidative phosphorylation and ROS as products of this process (Thannickal and Fanburg, 2000; Murphy, 2009; Zorov et al., 2014). The increase in ROS levels can lead to tissue damage and oxidative stress, and may underlie some of the deleterious consequences of chronic stress (Polidori et al., 2000). Our EE protocol attenuated the increase in trunk cortisol induced by UCS in zebrafish. It is arguable that the EE provides a perception of shelter, protection and security for zebrafish, contributing to a decreased activation of the neuroendocrine axis. However, ST-housed zebrafish may feel unprotected and vulnerable in a barren environment, and thus stay alert and respond more intensely to stress. Similarly, a study has recently found that EE during adolescence increased the amount of glucocorticoid receptors in the hippocampus and reduced circulating levels of corticosterone, improving the negative feedback of the neuroendocrine axis in rats from stressed strains (McCreary et al., 2016). At the same time, EE attenuated the increase in corticosterone after alcohol ingestion (Lopez and Laber, 2015) and decreased corticosterone production as measured by fecal corticosterone metabolites in mice (Gurfein et al., 2017). In this context, it is notable that EE influences the neuroendocrine axis and affects the production of glucocorticoids induced by different factors, in agreement with our study. However, this phenomenon is not yet fully understood, and more studies are needed to investigate the underlying mechanism.

Limitations of our study include the fact that correlations between biochemical and behavioral data could only be carried out for cortisol levels. Also, we only performed biochemical analysis at a single time point, i.e. after behavioral tests. Future studies are necessary to assess cortisol and ROS levels before and during the novel tank test. It would also be relevant to evaluate the effects of anti-oxidants and drugs able to block cortisol synthesis in order to test for mechanisms. Despite these limitations, our study extended the characterization of the UCS protocol, revealing that UCS increases ROS levels in the zebrafish brain. Also, we demonstrated that EE prevented this effect. The increase in ROS levels may lead to tissue damage and oxidative stress. These findings reinforce that environmental enrichment is a non-pharmacological neuromodulation strategy to protect against oxidative stress-related phenomena induced by UCS (Nithianantharajah and Hannan, 2006).

We have demonstrated for the first time that EE for 21 or 28 days promotes positive effects in zebrafish submitted to an unpredictable chronic stress protocol. Our results indicate that cortisol levels were correlated with anxiety levels, but future studies are required to address mechanistic relationships. We suggest that EE can be used as an alternative neuromodulatory strategy for reducing vulnerability to stress. This study also provides a new protocol to study the behavioral effects and neurobiological mechanisms involved in environmental enrichment.

FOOTNOTES

  • Competing interests

    The authors declare no competing or financial interests.

  • Author contributions

    Conceptualization: M.M., A.P.H., D.L., A.P.; Methodology: M.M., T.C., A.P.H., L.B., A.P.; Validation: A.P.; Formal analysis: M.M., R.M., R.B., A.P.H., G.K., A.P.; Writing - original draft: M.M., R.M., R.B., A.P.H., L.B., A.P.; Writing - review & editing: M.M., R.M., R.B., A.P.H., D.L., L.B., A.P.; Supervision: A.P.

  • Funding

    This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brazil (CNPq, Proc. 401162/2016-8) and CAPES.

  • Received December 28, 2017.
  • Accepted January 3, 2018.

References

  1. ↵
    1. Ali, S. F.,
    2. LeBel, C. P. and
    3. Bondy, S. C.
    (1992). Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13, 637-648.
    OpenUrlPubMedWeb of Science
  2. ↵
    1. Artola, A.,
    2. von Frijtag, J. C.,
    3. Fermont, P. C. J.,
    4. Gispen, W. H.,
    5. Schrama, L. H.,
    6. Kamal, A. and
    7. Spruijt, B. M.
    (2006). Long-lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment. Eur. J. Neurosci. 23, 261-272. doi:10.1111/j.1460-9568.2005.04552.x
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    1. Bardo, M. T.,
    2. Klebaur, J. E.,
    3. Valone, J. M. and
    4. Deaton, C.
    (2001). Environmental enrichment decreases intravenous self-administration of amphetamine in female and male rats. Psychopharmacology (Berl) 155, 278-284. doi:10.1007/s002130100720
    OpenUrlCrossRefPubMed
  4. ↵
    1. Bennett, E. L.,
    2. Diamond, M. C.,
    3. Krech, D. and
    4. Rosenzweig, M. R.
    (1964). Chemical and anatomical plasticity brain. Science 146, 610-619. doi:10.1126/science.146.3644.610
    OpenUrlFREE Full Text
  5. ↵
    1. Bezard, E.,
    2. Dovero, S.,
    3. Belin, D.,
    4. Duconger, S.,
    5. Jackson-Lewis, V.,
    6. Przedborski, S.,
    7. Piazza, P. V.,
    8. Gross, C. E. and
    9. Jaber, M.
    (2003). Enriched environment confers resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and cocaine: involvement of dopamine transporter and trophic factors. J. Neurosci. Off. J. Soc. Neurosci. 23, 10999-11007.
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Bhagya, V. R.,
    2. Srikumar, B. N.,
    3. Veena, J. and
    4. Shankaranarayana Rao, B. S.
    (2017). Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits. J. Neurosci. Res. 95, 1602-1610. doi:10.1002/jnr.23992
    OpenUrlCrossRef
  7. ↵
    1. Cechetti, F.,
    2. Worm, P. V.,
    3. Lovatel, G.,
    4. Moysés, F.,
    5. Siqueira, I. R. and
    6. Netto, C. A.
    (2012). Environmental enrichment prevents behavioral deficits and oxidative stress caused by chronic cerebral hypoperfusion in the rat. Life Sci. 91, 29-36. doi:10.1016/j.lfs.2012.05.013
    OpenUrlCrossRefPubMed
  8. ↵
    1. Chauvet, C.,
    2. Lardeux, V.,
    3. Goldberg, S. R.,
    4. Jaber, M. and
    5. Solinas, M.
    (2009). Environmental enrichment reduces cocaine seeking and reinstatement induced by cues and stress but not by cocaine. Neuropsychopharmacol 34, 2767-2778. doi:10.1038/npp.2009.127
    OpenUrlCrossRefPubMedWeb of Science
  9. ↵
    1. Crofton, E. J.,
    2. Zhang, Y. and
    3. Green, T. A.
    (2015). Inoculation stress hypothesis of environmental enrichment. Neurosci. Biobehav. Rev. 49, 19-31. doi:10.1016/j.neubiorev.2014.11.017
    OpenUrlCrossRef
  10. ↵
    1. DePasquale, C.,
    2. Neuberger, T.,
    3. Hirrlinger, A. M. and
    4. Braithwaite, V. A.
    (2016). The influence of complex and threatening environments in early life on brain size and behaviour. Proc. Biol. Sci. 283, 20152564. doi:10.1098/rspb.2015.2564
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Diamond, M. C.,
    2. Krech, D. and
    3. Rosenzweig, M. R.
    (1964). The effectsof an enriched environment on the histology of the rat cerebral cortex. J. Comp. Neurol. 123, 111-120. doi:10.1002/cne.901230110
    OpenUrlCrossRefPubMedWeb of Science
  12. ↵
    1. Egeland, M.,
    2. Zunszain, P. A. and
    3. Pariante, C. M.
    (2015). Molecular mechanisms in the regulation of adult neurogenesis during stress. Nat. Rev. Neurosci. 16, 189-200. doi:10.1038/nrn3855
    OpenUrlCrossRef
  13. ↵
    1. El Rawas, R.,
    2. Thiriet, N.,
    3. Lardeux, V.,
    4. Jaber, M. and
    5. Solinas, M.
    (2009). Environmental enrichment decreases the rewarding but not the activating effects of heroin. Psychopharmacology (Berl) 203, 561-570. doi:10.1007/s00213-008-1402-6
    OpenUrlCrossRefPubMedWeb of Science
  14. ↵
    1. Giacomini, A. C. V. V.,
    2. Abreu, M. S.,
    3. Zanandrea, R.,
    4. Saibt, N.,
    5. Friedrich, M. T.,
    6. Koakoski, G.,
    7. Gusso, D.,
    8. Piato, A. L. and
    9. Barcellos, L. J. G.
    (2016). Environmental and pharmacological manipulations blunt the stress response of zebrafish in a similar manner. Sci. Rep. 6, 28986. doi:10.1038/srep28986
    OpenUrlCrossRef
  15. ↵
    1. Green, T. A.,
    2. Alibhai, I. N.,
    3. Roybal, C. N.,
    4. Winstanley, C. A.,
    5. Theobald, D. E. H.,
    6. Birnbaum, S. G.,
    7. Graham, A. R.,
    8. Unterberg, S.,
    9. Graham, D. L.,
    10. Vialou, V. et al.
    (2010). Environmental enrichment produces a behavioral phenotype mediated by low cyclic adenosine monophosphate response element binding (CREB) activity in the nucleus accumbens. Biol. Psychiatry 67, 28-35. doi:10.1016/j.biopsych.2009.06.022
    OpenUrlCrossRefPubMedWeb of Science
  16. ↵
    1. Green, T. A.,
    2. Cain, M. E.,
    3. Thompson, M. and
    4. Bardo, M. T.
    (2003). Environmental enrichment decreases nicotine-induced hyperactivity in rats. Psychopharmacology (Berl) 170, 235-241. doi:10.1007/s00213-003-1538-3
    OpenUrlCrossRefPubMed
  17. ↵
    1. Gurfein, B. T.,
    2. Hasdemir, B.,
    3. Milush, J. M.,
    4. Touma, C.,
    5. Palme, R.,
    6. Nixon, D. F.,
    7. Darcel, N.,
    8. Hecht F. M. and
    9. Bhargava, A.
    (2017). Enriched environment and stress exposure influence splenic B lymphocyte composition. PloS One 12, e0180771. doi:10.1371/journal.pone.0180771
    OpenUrlCrossRef
  18. ↵
    1. Gutierrez, J.,
    2. Ballinger, S. W.,
    3. Darley-Usmar, V. M. and
    4. Landar, A.
    (2006). Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ. Res. 99, 924-932. doi:10.1161/01.RES.0000248212.86638.e9
    OpenUrlAbstract/FREE Full Text
  19. ↵
    1. Kirschbaum, C.,
    2. Pirke, K.-M. and
    3. Hellhammer, D. H.
    (1993). The ‘Trier Social Stress Test’ – a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28, 76-81. doi:10.1159/000119004
    OpenUrlCrossRefPubMedWeb of Science
  20. ↵
    1. Kysil, E. V.,
    2. Meshalkina, D. A.,
    3. Frick, E. E.,
    4. Echevarria, D. J.,
    5. Rosemberg, D. B.,
    6. Maximino, C.,
    7. Lima, M. G.,
    8. Abreu, M. S.,
    9. Giacomini, A. C.,
    10. Barcellos, L. J. G. et al.
    (2017). Comparative analyses of zebrafish anxiety-like behavior using conflict-based novelty tests. Zebrafish 14, 197-208. doi:10.1089/zeb.2016.1415
    OpenUrlCrossRef
  21. ↵
    1. Lazarov, O.,
    2. Robinson, J.,
    3. Tang, Y.-P.,
    4. Hairston, I. S.,
    5. Korade-Mirnics, Z.,
    6. Lee, V. M.-Y.,
    7. Hersh, L. B.,
    8. Sapolsky, R. M.,
    9. Mirnics, K. and
    10. Sisodia, S. S.
    (2005). Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. Cell 120, 701-713. doi:10.1016/j.cell.2005.01.015
    OpenUrlCrossRefPubMedWeb of Science
  22. ↵
    1. LeBel, C. P.,
    2. Ali, S. F.,
    3. McKee, M. and
    4. Bondy, S. C.
    (1990). Organometal-induced increases in oxygen reactive species: the potential of 2’,7’-dichlorofluorescin diacetate as an index of neurotoxic damage. Toxicol. Appl. Pharmacol. 104, 17-24. doi:10.1016/0041-008X(90)90278-3
    OpenUrlCrossRefPubMedWeb of Science
  23. ↵
    1. Lopez, M. F. and
    2. Laber, K.
    (2015). Impact of social isolation and enriched environment during adolescence on voluntary ethanol intake and anxiety in C57BL/6J mice. Physiol. Behav. 148, 151-156. doi:10.1016/j.physbeh.2014.11.012
    OpenUrlCrossRef
  24. ↵
    1. Manuel, R.,
    2. Gorissen, M.,
    3. Stokkermans, M.,
    4. Zethof, J.,
    5. Ebbesson, L. O. E.,
    6. van de Vis, H.,
    7. Flik, G. and
    8. van den Bos, R.
    (2015). The effects of environmental enrichment and age-related differences on inhibitory avoidance in zebrafish (Danio rerio Hamilton). Zebrafish 12, 152-165. doi:10.1089/zeb.2014.1045
    OpenUrlCrossRef
  25. ↵
    1. Marcon, M.,
    2. Herrmann, A. P.,
    3. Mocelin, R.,
    4. Rambo, C. L.,
    5. Koakoski, G.,
    6. Abreu, M. S.,
    7. Conterato, G. M. M.,
    8. Kist, L. W.,
    9. Bogo, M. R.,
    10. Zanatta, L. et al.
    (2016). Prevention of unpredictable chronic stress-related phenomena in zebrafish exposed to bromazepam, fluoxetine and nortriptyline. Psychopharmacology (Berl.) 233, 3815-3824.
    OpenUrl
  26. ↵
    1. McCreary, J. K.,
    2. Erickson, Z. T.,
    3. Hao, Y. X.,
    4. Ilnytskyy, Y.,
    5. Kovalchuk, I. and
    6. Metz, G. A. S.
    (2016). Environmental intervention as a therapy for adverse programming by ancestral stress. Sci. Rep. 6, 37814. doi:10.1038/srep37814
    OpenUrlCrossRef
  27. ↵
    1. McEwen, B. S.,
    2. Bowles, N. P.,
    3. Gray, J. D.,
    4. Hill, M. N.,
    5. Hunter, R. G.,
    6. Karatsoreos, I. N. and
    7. Nasca, C.
    (2015). Mechanisms of stress in the brain. Nat. Neurosci. 18, 1353-1363. doi:10.1038/nn.4086
    OpenUrlCrossRefPubMed
  28. ↵
    1. Miklós, I. H. and
    2. Kovács, K. J.
    (2012). Reorganization of synaptic inputs to the hypothalamic paraventricular nucleus during chronic psychogenic stress in rats. Biol. Psychiatry 71, 301-308. doi:10.1016/j.biopsych.2011.10.027
    OpenUrlCrossRefPubMedWeb of Science
  29. ↵
    1. Murphy, M. P.
    (2009). How mitochondria produce reactive oxygen species. Biochem. J. 417, 1-13. doi:10.1042/BJ20081386
    OpenUrlAbstract/FREE Full Text
  30. ↵
    1. Nithianantharajah, J. and
    2. Hannan, A. J.
    (2006). Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat. Rev. Neurosci. 7, 697-709. doi:10.1038/nrn1970
    OpenUrlCrossRefPubMedWeb of Science
  31. ↵
    1. Otte, C.,
    2. Gold, S. M.,
    3. Penninx, B. W.,
    4. Pariante, C. M.,
    5. Etkin, A.,
    6. Fava, M.,
    7. Mohr, D. C. and
    8. Schatzberg, A. F.
    (2016). Major depressive disorder. Nat. Rev. Dis. Primer 2, 16065. doi:10.1038/nrdp.2016.65
    OpenUrlCrossRef
  32. ↵
    1. Pang, T. Y. C. and
    2. Hannan, A. J.
    (2013). Enhancement of cognitive function in models of brain disease through environmental enrichment and physical activity. Neuropharmacology 64, 515-528. doi:10.1016/j.neuropharm.2012.06.029
    OpenUrlCrossRef
  33. ↵
    1. Parker, M. O.,
    2. Millington, M. E.,
    3. Combe, F. J. and
    4. Brennan, C. H.
    (2012). Housing conditions differentially affect physiological and behavioural stress responses of zebrafish, as well as the response to anxiolytics. PloS One 7, e34992. doi:10.1371/journal.pone.0034992
    OpenUrlCrossRefPubMed
  34. ↵
    1. Piato, Â. L.,
    2. Capiotti, K. M.,
    3. Tamborski, A. R.,
    4. Oses, J. P.,
    5. Barcellos, L. J. G.,
    6. Bogo, M. R.,
    7. Lara, D. R.,
    8. Vianna, M. R. and
    9. Bonan, C. D.
    (2011). Unpredictable chronic stress model in zebrafish (Danio rerio): behavioral and physiological responses. Prog. Neuropsychopharmacol. Biol. Psychiatry 35, 561-567. doi:10.1016/j.pnpbp.2010.12.018
    OpenUrlCrossRefPubMed
  35. ↵
    1. Polidori, M. C.,
    2. Mecocci, P.,
    3. Cherubini, A. and
    4. Senin, U.
    (2000). Physical activity and oxidative stress during aging. Int. J. Sports Med. 21, 154-157. doi:10.1055/s-2000-8881
    OpenUrlCrossRefPubMedWeb of Science
  36. ↵
    1. Rambo, C. L.,
    2. Mocelin, R.,
    3. Marcon, M.,
    4. Villanova, D.,
    5. Koakoski, G.,
    6. de Abreu, M. S.,
    7. Oliveira, T. A.,
    8. Barcellos, L. J. G.,
    9. Piato, A. L. and
    10. Bonan, C. D.
    (2017). Gender differences in aggression and cortisol levels in zebrafish subjected to unpredictable chronic stress. Physiol. Behav. 171, 50-54. doi:10.1016/j.physbeh.2016.12.032
    OpenUrlCrossRef
  37. ↵
    1. Rampon, C.,
    2. Jiang, C. H.,
    3. Dong, H.,
    4. Tang, Y.-P.,
    5. Lockhart, D. J.,
    6. Schultz, P. G.,
    7. Tsien, J. Z. and
    8. Hu, Y.
    (2000). Effects of environmental enrichment on gene expression in the brain. Proc. Natl. Acad. Sci. 97, 12880-12884. doi:10.1073/pnas.97.23.12880
    OpenUrlAbstract/FREE Full Text
  38. ↵
    1. Sampedro-Piquero, P.,
    2. Begega, A. and
    3. Arias, J. L.
    (2014). Increase of glucocorticoid receptor expression after environmental enrichment: relations to spatial memory, exploration and anxiety-related behaviors. Physiol. Behav. 129, 118-129. doi:10.1016/j.physbeh.2014.02.048
    OpenUrlCrossRef
  39. ↵
    1. Schroeder, P.,
    2. Jones, S.,
    3. Young, I. S. and
    4. Sneddon, L. U.
    (2014). What do zebrafish want? Impact of social grouping, dominance and gender on preference for enrichment. Lab. Anim. 48, 328-337. doi:10.1177/0023677214538239
    OpenUrlCrossRefPubMed
  40. ↵
    1. Shams, S.,
    2. Chatterjee, D. and
    3. Gerlai, R.
    (2015). Chronic social isolation affects thigmotaxis and whole-brain serotonin levels in adult zebrafish. Behav. Brain Res. 292, 283-287. doi:10.1016/j.bbr.2015.05.061
    OpenUrlCrossRef
  41. ↵
    1. Shilpa, B. M.,
    2. Bhagya, V.,
    3. Harish, G.,
    4. Srinivas Bharath, M. M. and
    5. Shankaranarayana Rao, B. S.
    (2017). Environmental enrichment ameliorates chronic immobilisation stress-induced spatial learning deficits and restores the expression of BDNF, VEGF, GFAP and glucocorticoid receptors. Prog. Neuropsychopharmacol. Biol. Psychiatry 76, 88-100. doi:10.1016/j.pnpbp.2017.02.025
    OpenUrlCrossRef
  42. ↵
    1. Solinas, M.,
    2. Chauvet, C.,
    3. Thiriet, N.,
    4. El Rawas, R. and
    5. Jaber, M.
    (2008). Reversal of cocaine addiction by environmental enrichment. Proc. Natl. Acad. Sci. USA 105, 17145-17150. doi:10.1073/pnas.0806889105
    OpenUrlAbstract/FREE Full Text
  43. ↵
    1. Solinas, M.,
    2. Thiriet, N.,
    3. Rawas, R. E.,
    4. Lardeux, V. and
    5. Jaber, M.
    (2009). Environmental enrichment during early stages of life reduces the behavioral, neurochemical, and molecular effects of cocaine. Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol. 34, 1102-1111. doi:10.1038/npp.2008.51
    OpenUrlCrossRefPubMedWeb of Science
  44. ↵
    1. Song, C.,
    2. Liu, B.-P.,
    3. Zhang, Y.-P.,
    4. Peng, Z.,
    5. Wang, J.,
    6. Collier, A. D.,
    7. Echevarria, D. J.,
    8. Savelieva, K. V.,
    9. Lawrence, R. F.,
    10. Rex, C. S. et al.
    (2017). Modeling consequences of prolonged strong unpredictable stress in zebrafish: complex effects on behavior and physiology. Prog. Neuropsychopharmacol. Biol. Psychiatry. 81, 384-394. doi:10.1016/j.pnpbp.2017.08.021
    OpenUrlCrossRef
  45. ↵
    1. Stairs, D. J. and
    2. Bardo, M. T.
    (2009). Neurobehavioral effects of environmental enrichment and drug abuse vulnerability. Pharmacol. Biochem. Behav. 92, 377-382. doi:10.1016/j.pbb.2009.01.016
    OpenUrlCrossRefPubMed
  46. ↵
    1. Sun, X. R.,
    2. Zhang, H.,
    3. Zhao, H. T.,
    4. Ji, M. H.,
    5. Li, H. H.,
    6. Wu, J.,
    7. Li, K. Y. and
    8. Yang, J. J.
    (2016). Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder. Behav. Brain Res. 312, 84-92. doi:10.1016/j.bbr.2016.06.016
    OpenUrlCrossRef
  47. ↵
    1. Tanti, A.,
    2. Westphal, W.-P.,
    3. Girault, V.,
    4. Brizard, B.,
    5. Devers, S.,
    6. Leguisquet, A.-M.,
    7. Surget, A. and
    8. Belzung, C.
    (2013). Region-dependent and stage-specific effects of stress, environmental enrichment, and antidepressant treatment on hippocampal neurogenesis. Hippocampus 23, 797-811. doi:10.1002/hipo.22134
    OpenUrlCrossRefPubMedWeb of Science
  48. ↵
    1. Thannickal, V. J. and
    2. Fanburg, B. L.
    (2000). Reactive oxygen species in cell signaling. Am. J. Physiol. - Lung Cell. Mol. Physiol. 279, L1005-L1028. doi:10.1152/ajplung.2000.279.6.L1005
    OpenUrlCrossRef
  49. ↵
    1. Urakawa, S.,
    2. Mitsushima, D.,
    3. Shimozuru, M.,
    4. Sakuma, Y. and
    5. Kondo, Y.
    (2014). An enriched rearing environment calms adult male rat sexual activity: implication for distinct serotonergic and hormonal responses to females. PloS One 9, e87911. doi:10.1371/journal.pone.0087911
    OpenUrlCrossRef
  50. ↵
    1. van Praag, H.,
    2. Kempermann, G. and
    3. Gage, F. H.
    (2000). Neural consequences of environmental enrichment. Nat. Rev. Neurosci. 1, 191-198. doi:10.1038/35044558
    OpenUrlCrossRefPubMedWeb of Science
  51. ↵
    1. Veena, J.,
    2. Srikumar, B. N.,
    3. Mahati, K.,
    4. Bhagya, V.,
    5. Raju, T. R. and
    6. Shankaranarayana Rao, B. S.
    (2009). Enriched environment restores hippocampal cell proliferation and ameliorates cognitive deficits in chronically stressed rats. J. Neurosci. Res. 87, 831-843. doi:10.1002/jnr.21907
    OpenUrlCrossRefPubMed
  52. ↵
    1. Vega-Rivera, N. M.,
    2. Ortiz-López, L.,
    3. Gómez-Sánchez, A.,
    4. Oikawa-Sala, J.,
    5. Estrada-Camarena, E. M. and
    6. Ramírez-Rodríguez, G. B.
    (2016). The neurogenic effects of an enriched environment and its protection against the behavioral consequences of chronic mild stress persistent after enrichment cessation in six-month-old female Balb/C mice. Behav. Brain Res. 301, 72-83. doi:10.1016/j.bbr.2015.12.028
    OpenUrlCrossRefPubMed
  53. ↵
    1. von Krogh, K.,
    2. Sørensen, C.,
    3. Nilsson, G. E. and
    4. Øverli, Ø.
    (2010). Forebrain cell proliferation, behavior, and physiology of zebrafish, Danio rerio, kept in enriched or barren environments. Physiol. Behav. 101, 32-39. doi:10.1016/j.physbeh.2010.04.003
    OpenUrlCrossRefPubMedWeb of Science
    1. Westerfield, M.
    (2000). The Zebrafish Book. A Guide for the Laboratory use of Zebrafish (Danio Rerio). 4th edn. Eugene: University of Oregon Press.
  55. ↵
    1. Young, D.,
    2. Lawlor, P. A.,
    3. Leone, P.,
    4. Dragunow, M. and
    5. During, M. J.
    (1999). Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nat. Med. 5, 448-453. doi:10.1038/7449
    OpenUrlCrossRefPubMedWeb of Science
  56. ↵
    1. Zhu, J.,
    2. Apparsundaram, S.,
    3. Bardo, M. T. and
    4. Dwoskin, L. P.
    (2005). Environmental enrichment decreases cell surface expression of the dopamine transporter in rat medial prefrontal cortex. J. Neurochem. 93, 1434-1443. doi:10.1111/j.1471-4159.2005.03130.x
    OpenUrlCrossRefPubMedWeb of Science
  57. ↵
    1. Zorov, D. B.,
    2. Juhaszova, M. and
    3. Sollott, S. J.
    (2014). Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev. 94, 909-950. doi:10.1152/physrev.00026.2013
    OpenUrlCrossRefPubMed
View Abstract
Back to top

Keywords

 Download PDF

Email
Research Article
Environmental enrichment modulates the response to chronic stress in zebrafish
Matheus Marcon, Ricieri Mocelin, Radharani Benvenutti, Tales Costa, Ana P. Herrmann, Diogo L. de Oliveira, Gessi Koakoski, Leonardo J. G. Barcellos, Angelo Piato
Journal of Experimental Biology 2018 221: jeb176735 doi: 10.1242/jeb.176735 Published 22 February 2018
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

The Company of Biologists commits to the Transformative Journal approach

The Company of Biologists is the first not-for-profit publisher to commit to this approach. The Company's three hybrid journals - Development, Journal of Cell Science and Journal of Experimental Biology - have chosen the 'transformative' route towards Open Access. Find out more in this interview with Claire Moulton, Publisher at The Company of Biologists and on our dedicated Transformative Journals page.

Handing over the reins

Photo of Hans Hoppeler and Craig Franklin

The start of August signals a change for Journal of Experimental Biology as we say a fond farewell to Editor-in-Chief of 25 years Hans Hoppeler and extend a warm welcome to his successor, Craig Franklin.

Minute mecysmaucheniid spider triggers fastest trap-jaws

Research by Hannah Wood shows that Zearchaea spiders use a spring loaded catapult mechanism to slam closed the fastest spider jaws on the planet, at an astonishing speed of 18.2 m s−1.

In the field: an interview with Sandra Binning and Dominique Roche

Photo of Sarah Binning and Dominique Roche

Together, Sandra Binning and Dominique Roche investigate how animals respond to environmental stress. In an interview, they talk about taking their children into the field and keeping safe while working in marine locations.

Surviving anoxia: the maintenance of energy production and tissue integrity during anoxia and reoxygenation

In their Review, Georgina Cox and Todd Gillis use knowledge gained from studies of anoxia-tolerant species to identify common strategies and novel solutions for the challenges of anoxia exposure.