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Article ; Online: Age-dependent effects of embryonic ethanol exposure on anxiety-like behaviours in young zebrafish: A genotype comparison study.

Facciol, Amanda / Marawi, Tulip / Syed, Erum / Gerlai, Robert

Pharmacology, biochemistry, and behavior

2022 Volume 214, Page(s) 173342

Abstract: Fetal Alcohol Spectrum Disorder (FASD) is characterized by a variety of morphological, behavioural and cognitive deficits, ranging from mild to severe. Numerous animal models, including the zebrafish, have been employed to better understand the onset, ... ...

Abstract	Fetal Alcohol Spectrum Disorder (FASD) is characterized by a variety of morphological, behavioural and cognitive deficits, ranging from mild to severe. Numerous animal models, including the zebrafish, have been employed to better understand the onset, expression and progression of this disorder. Embryonic ethanol-induced deficits in learning and memory, anxiety, social responses and elevated alcohol self-administration have been successfully demonstrated in zebrafish. Studies in zebrafish have also shown the expression of these behavioural deficits depends upon the developmental stage of ethanol exposure, the age of observation, as well as the genotype (strain or population origin) of the tested zebrafish. Here, we investigate how the genotype and age of observation may influence embryonic ethanol-induced alterations in anxiety-like responses in zebrafish. Zebrafish embryos exposed to either 0% or 1% (vol/vol) ethanol at 24hpf were tested in an open tank at one of three stages: larval (6-8 days post fertilization (dpf)), mid-larval (16-18dpf), or juvenile (26-28dpf). Two genotypes were tested in this manner, AB
MeSH term(s)	Animals ; Anxiety/chemically induced ; Anxiety/genetics ; Disease Models, Animal ; Ethanol/pharmacology ; Female ; Fetal Alcohol Spectrum Disorders/metabolism ; Fetal Alcohol Spectrum Disorders/psychology ; Genotype ; Humans ; Larva ; Pregnancy ; Zebrafish/genetics
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2022-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	191042-5
ISSN	1873-5177 ; 0091-3057
ISSN (online)	1873-5177
ISSN	0091-3057
DOI	10.1016/j.pbb.2022.173342
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Article: Zebrafish Shoaling, Its Behavioral and Neurobiological Mechanisms, and Its Alteration by Embryonic Alcohol Exposure: A Review.

Facciol, Amanda / Gerlai, Robert

Frontiers in behavioral neuroscience

2020 Volume 14, Page(s) 572175

Abstract: Social cognition and social behaviors are complex phenomena that involve numerous brain areas and underlying neurobiological mechanisms. Embryonic alcohol exposure may lead to the development of Fetal Alcohol Spectrum Disorder (FASD), a disorder that ... ...

Abstract	Social cognition and social behaviors are complex phenomena that involve numerous brain areas and underlying neurobiological mechanisms. Embryonic alcohol exposure may lead to the development of Fetal Alcohol Spectrum Disorder (FASD), a disorder that manifests with varying symptoms including abnormal social behavior and other cognitive deficits. Animal models have been utilized to mimic aspects of the disease and to study potential underlying mechanisms. The zebrafish is a relative newcomer in this field but has been suggested as an optimal compromise between system complexity and practical simplicity for modeling FASD. Importantly, due to external fertilization and development of the embryo outside the mother and subsequent lack of parental care, this species allows precise control of the timing and dose of alcohol delivery during embryonic development. Furthermore, the zebrafish is a highly social species and thus may be particularly appropriate for the analysis of embryonic alcohol-induced alterations in this context. Here, we provide a succinct review focusing on shoaling, a prominent form of social behavior, in zebrafish. We summarize what is known about its behavioral mechanisms and underlying neurobiological processes, and how it is altered by exposure to ethanol during embryonic development. Lastly, we briefly consider possible future directions of research that would help us better understand the relationship between the behavioral expression and molecular basis of embryonic ethanol-induced social deficits in fish and humans.
Language	English
Publishing date	2020-09-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452960-6
ISSN	1662-5153
ISSN	1662-5153
DOI	10.3389/fnbeh.2020.572175
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Article ; Online: Inflammatory Pain Alters Dopaminergic Modulation of Excitatory Synapses in the Anterior Cingulate Cortex of Mice.

Darvish-Ghane, Soroush / Lyver, Brendan / Facciol, Amanda / Chatterjee, Diptendu / Martin, Loren J

Neuroscience

2022 Volume 498, Page(s) 249–259

Abstract: Pain modulation of dopamine-producing nuclei is known to contribute to the affective component of chronic pain. However, pain modulation of pain-related cortical regions receiving dopaminergic inputs is understudied. The present study demonstrates that ... ...

Abstract	Pain modulation of dopamine-producing nuclei is known to contribute to the affective component of chronic pain. However, pain modulation of pain-related cortical regions receiving dopaminergic inputs is understudied. The present study demonstrates that mice with chronic inflammatory injury of the hind paws develop persistent mechanical hypersensitivity and transient anxiety. Peripheral inflammation induced by injection of complete Freund's Adjuvant (CFA) induced potentiation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) currents with a presynaptic component in layer II/III of the ACC. After four days of inflammatory pain, the dopamine-mediated inhibition of AMPAR currents was significantly reduced in the ACC. Furthermore, dopamine enhanced presynaptic modulation of excitatory transmission, but only in mice with inflammatory pain. High-performance liquid chromatography (HPLC) analysis of dopamine tissue concentration revealed that dopamine neurotransmitter concentration in the ACC was reduced three days following CFA. Our results demonstrate that inflammatory pain induces activity-dependent changes in excitatory synaptic transmission and alters dopaminergic homeostasis in the ACC.
MeSH term(s)	Animals ; Chronic Pain ; Dopamine ; Freund's Adjuvant ; Gyrus Cinguli ; Inflammation ; Mice ; Mice, Inbred C57BL ; Synapses ; Synaptic Transmission
Chemical Substances	Freund's Adjuvant (9007-81-2) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-07-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2022.07.010
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Article ; Online: A Standardized Tank Design for the Light Dark Task in Zebrafish.

Facciol, Amanda / Tran, Steven / Gerlai, Robert

Bio-protocol

2019 Volume 9, Issue 14, Page(s) e3306

Abstract: The light dark paradigm is a common behavioral test used to screen a variety of pharmacological agents, including anxiogenics and anxiolytics. Although most often used in rodents, the light dark task has recently been adapted for use in zebrafish. ... ...

Abstract	The light dark paradigm is a common behavioral test used to screen a variety of pharmacological agents, including anxiogenics and anxiolytics. Although most often used in rodents, the light dark task has recently been adapted for use in zebrafish. However, a number of inconsistent findings have been reported for this species. Some have found zebrafish to prefer black, while others report a preference for light. Careful analysis of light dark preference experiments using zebrafish reveals significant variation in testing tank design and test conditions, including lighting and substrate color. Additionally, in some experiments the designated dark side of the testing tank is completely covered, producing a "cave-like" environment which further confounds results. Lastly, authors commonly use the terms "light vs. dark" interchangeably with "white vs. black", when these are two separate factors that may influence preference: illumination level vs. background shade. To address these limitations, we designed testing tanks that differentiate illumination vs. background shade preference in zebrafish. This design allows for simple standardization of light dark testing apparatus in zebrafish, and facilitates more reliable comparison across studies.
Language	English
Publishing date	2019-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.3306
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Article ; Online: Alcohol exposure during embryonic development: An opportunity to conduct systematic developmental time course analyses in zebrafish.

Facciol, Amanda / Tsang, Benjamin / Gerlai, Robert

Neuroscience and biobehavioral reviews

2019 Volume 98, Page(s) 185–193

Abstract: Ethanol affects numerous neurobiological processes depending upon the developmental stage at which it reaches the vertebrate embryo. Exposure time dependency may explain the variable severity and manifestation of life-long symptoms observed in fetal ... ...

Abstract	Ethanol affects numerous neurobiological processes depending upon the developmental stage at which it reaches the vertebrate embryo. Exposure time dependency may explain the variable severity and manifestation of life-long symptoms observed in fetal alcohol spectrum disorder (FASD) patients. Characterization of behavioural deficits will help us understand developmental stage-dependency and its underlying biological mechanisms. Here we highlight pioneering studies that model FASD using zebrafish, including those that demonstrated developmental stage-dependency of alcohol effects on some behaviours. We also succinctly review the more expansive mammalian literature, briefly discuss potential developmental stage dependent biological mechanisms alcohol alters, and review some of the disadvantages of mammalian systems versus the zebrafish. We stress that the temporal control of alcohol administration in the externally developing zebrafish gives unprecedented precision and is a major advantage of this species over other model organisms employed so far. We also emphasize that the zebrafish is well suited for high throughput screening and will allow systematic exploration of embryonic-stage dependent alcohol effects via mutagenesis and drug screens.
MeSH term(s)	Animals ; Behavior, Animal/physiology ; Disease Models, Animal ; Ethanol/pharmacology ; Fetal Alcohol Spectrum Disorders/etiology ; Humans ; Learning/drug effects ; Learning/physiology ; Zebrafish/embryology
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2019-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2019.01.012
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Zs.A 1371: Show issues

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Article ; Online: Developmental stage-dependent deficits induced by embryonic ethanol exposure in zebrafish: A neurochemical analysis.

Facciol, Amanda / Bailleul, Celine / Nguyen, Samuel / Chatterjee, Diptendu / Gerlai, Robert

Progress in neuro-psychopharmacology & biological psychiatry

2020 Volume 99, Page(s) 109859

Abstract: FASD results from the developing fetus being exposed to alcohol, and is characterized by morphological, behavioural and cognitive deficits. However, the expression, severity and age of onset of these symptoms has been found to show variation. This ... ...

Abstract	FASD results from the developing fetus being exposed to alcohol, and is characterized by morphological, behavioural and cognitive deficits. However, the expression, severity and age of onset of these symptoms has been found to show variation. This variation may partly be due to the developmental stage at which alcohol reached the developing fetus. Previously, alcohol was shown to lead to significant concentration dependent behavioural as well as neurochemical changes detected in adult zebrafish when this substance was administered at 24 h post-fertilization (hpf) for 2 h. This alcohol exposure method arguably mimicked the milder, and more prevalent, forms of human FASD. However, whether the observed changes depended upon the developmental stage, i.e., the timing, of alcohol exposure has not been systematically analyzed. Here, we employ the same alcohol dosing regimen, where zebrafish eggs are immersed into 0% or 1% (vol/vol) alcohol for 2 h, but we perform the immersion at 5, 10, 16, 24, 36, or 48 hpf. We previously developed a sensitive HPLC method to quantify neurochemicals, and found levels of dopamine, serotonin and their metabolites DOPAC and 5-HIAA to be affected by embryonic alcohol treatment. Here, using the same method, we compare whole-brain levels of these neurochemicals in the embryonic alcohol exposed and control zebrafish at their age of 30 days post-fertilization (dpf). Consistent with previous reports, we found significant reduction of levels of dopamine, serotonin and their metabolites in the fish exposed to alcohol at 24 hpf. However, we also found significant dependency on the developmental stage at which alcohol was administered with particularly robust impairments when the exposure was at the early or middle of the developmental periods probed. Our results now demonstrate that one can detect functional abnormalities in the zebrafish brain induced by embryonic alcohol as early as 30 dpf and that the neurochemical deficits are dependent upon the developmental stage at which alcohol is administered.
MeSH term(s)	3,4-Dihydroxyphenylacetic Acid/metabolism ; Animals ; Brain/drug effects ; Brain/embryology ; Brain/metabolism ; Dopamine/metabolism ; Ethanol/toxicity ; Female ; Fetal Alcohol Spectrum Disorders/metabolism ; Hydroxyindoleacetic Acid/metabolism ; Male ; Pregnancy ; Zebrafish
Chemical Substances	3,4-Dihydroxyphenylacetic Acid (102-32-9) ; Ethanol (3K9958V90M) ; Hydroxyindoleacetic Acid (54-16-0) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2020-01-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	781181-0
ISSN	1878-4216 ; 0278-5846
ISSN (online)	1878-4216
ISSN	0278-5846
DOI	10.1016/j.pnpbp.2020.109859
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Zs.A 1342: Show issues

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Article ; Online: The light-dark task in zebrafish confuses two distinct factors: Interaction between background shade and illumination level preference.

Facciol, Amanda / Iqbal, Mahrukh / Eada, Aishwarya / Tran, Steven / Gerlai, Robert

Pharmacology, biochemistry, and behavior

2019 Volume 179, Page(s) 9–21

Abstract: The light-dark preference task has been commonly used in rodents to screen for anxiogenic and anxiolytic drugs. However, recent adaptations of the light-dark preference test for zebrafish have produced inconsistent results. Several studies have reported ... ...

Abstract	The light-dark preference task has been commonly used in rodents to screen for anxiogenic and anxiolytic drugs. However, recent adaptations of the light-dark preference test for zebrafish have produced inconsistent results. Several studies have reported that zebrafish exhibit a preference for light, while others have found a preference for black. We suggest the inconsistencies may be the result of confusing certain parameters of the test leading to improper interpretation. For example, researchers often use "light" interchangeably with "white" and "dark" with "black" when these are two distinct factors: level of illumination vs. background shade. In the current study, we use specifically designed preference tanks to investigate the influence of background shade (i.e. white vs. black) and level of illumination (i.e. light vs. dark) on preference and anxiety-like behaviour. Furthermore, we pharmacologically validate our results by quantifying the effects of ethanol, a drug with known anxiety-altering properties, on anxiety-like behaviours. Here we report that zebrafish's preference varies depending upon background shade and level of illumination. We also found that ethanol administration altered behavioural responses in an illumination- and background shade-dependent manner. Our findings reinforce the need to correctly differentiate between these factors when interpreting results obtained with this behavioural paradigm. Lastly, our results show that simple modifications to the experimental tank in which anxiety-related responses are measured can significantly alter behaviour of zebrafish, supporting the need for standardized testing procedures and/or for detailed description of experimental procedures and the apparatus.
MeSH term(s)	Animals ; Anxiety/chemically induced ; Anxiety/physiopathology ; Behavior, Animal ; Darkness ; Ethanol/adverse effects ; Female ; Lighting ; Male ; Zebrafish/physiology
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2019-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	191042-5
ISSN	1873-5177 ; 0091-3057
ISSN (online)	1873-5177
ISSN	0091-3057
DOI	10.1016/j.pbb.2019.01.006
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Zs.A 1060: Show issues

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Article ; Online: Acute administration of a dopamine D2/D3 receptor agonist alters behavioral and neural parameters in adult zebrafish.

Nabinger, Débora Dreher / Altenhofen, Stefani / Buatois, Alexis / Facciol, Amanda / Peixoto, Julia Vasconcellos / da Silva, Julia Maria Kuhl / Chatterjee, Diptendu / Rübensam, Gabriel / Gerlai, Robert / Bonan, Carla Denise

Progress in neuro-psychopharmacology & biological psychiatry

2023 Volume 125, Page(s) 110753

Abstract: The dopaminergic neurotransmitter system is implicated in several brain functions and behavioral processes. Alterations in it are associated with the pathogenesis of several human neurological disorders. Pharmacological agents that interact with the ... ...

Abstract	The dopaminergic neurotransmitter system is implicated in several brain functions and behavioral processes. Alterations in it are associated with the pathogenesis of several human neurological disorders. Pharmacological agents that interact with the dopaminergic system allow the investigation of dopamine-mediated cellular and molecular responses and may elucidate the biological bases of such disorders. Zebrafish, a translationally relevant biomedical research organism, has been successfully employed in prior psychopharmacology studies. Here, we evaluated the effects of quinpirole (dopamine D2/D3 receptor agonist) in adult zebrafish on behavioral parameters, brain-derived neurotrophic factor (BDNF) and neurotransmitter levels. Zebrafish received intraperitoneal injections of 0.5, 1.0, or 2.0 mg/kg quinpirole or saline (control group) twice with an inter-injection interval of 48 h. All tests were performed 24 h after the second injection. After this acute quinpirole administration, zebrafish exhibited decreased locomotor activity, increased anxiety-like behaviors and memory impairment. However, quinpirole did not affect social and aggressive behavior. Quinpirole-treated fish exhibited stereotypic swimming, characterized by repetitive behavior followed by immobile episodes. Moreover, quinpirole treatment also decreased the number of BDNF-immunoreactive cells in the zebrafish brain. Analysis of neurotransmitter levels demonstrated a significant increase in glutamate and a decrease in serotonin, while no alterations were observed in dopamine. These findings demonstrate that dopaminergic signaling altered by quinpirole administration results in significant behavioral and neuroplastic changes in the central nervous system of zebrafish. Thus, we conclude that the use of quinpirole administration in adult zebrafish may be an appropriate tool for the analysis of mechanisms underlying neurological disorders related to the dopaminergic system.
MeSH term(s)	Animals ; Humans ; Dopamine Agonists/pharmacology ; Quinpirole/pharmacology ; Zebrafish ; Receptors, Dopamine D3 ; Dopamine/pharmacology ; Brain-Derived Neurotrophic Factor ; Motor Activity
Chemical Substances	Dopamine Agonists ; Quinpirole (20OP60125T) ; Receptors, Dopamine D3 ; Dopamine (VTD58H1Z2X) ; Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2023-03-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	781181-0
ISSN	1878-4216 ; 0278-5846
ISSN (online)	1878-4216
ISSN	0278-5846
DOI	10.1016/j.pnpbp.2023.110753
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Article ; Online: Re-examining the factors affecting choice in the light-dark preference test in zebrafish.

Facciol, Amanda / Tran, Steven / Gerlai, Robert

Behavioural brain research

2017 Volume 327, Page(s) 21–28

Abstract: The light-dark preference test has been extensively used to screen anxiolytic drugs and investigate mechanisms of anxiety with rodents. Recently, this task has been adapted to zebrafish, but a number of inconsistent findings have emerged. For example, ... ...

Abstract	The light-dark preference test has been extensively used to screen anxiolytic drugs and investigate mechanisms of anxiety with rodents. Recently, this task has been adapted to zebrafish, but a number of inconsistent findings have emerged. For example, some found zebrafish to avoid and others to prefer dark. Given the translational relevance of the zebrafish, its utility in high throughput drug screens, and that anxiety still represents a large unmet medical need, there is an urgent need to resolve these inconsistencies. We propose these inconsistencies are due to lack of distinction between two separate factors: background shade and level of illumination. Here, we systematically manipulated background shade (black vs. white) while keeping the illumination level constant (uniformly illuminated). We also manipulated the level of illumination (illuminated vs. not illuminated) while keeping the background constant (either uniformly black or white). We examined the time-course of numerous behavioural responses under these conditions, and found zebrafish to exhibit a significant preference for the black side of the tank within the first 3min of the test when the illumination level was constant. We found this response, along with other anxiety-like behaviours, to diminish over time. In contrast, we found zebrafish did not exhibit a preference for the unilluminated (dark) side of the tank when the background shade was kept constant. Our results demonstrate a dissociation between illumination level and background shade, shown by a preference for black to white, but not for dark to light, confirming the importance of differentiating these two distinct factors.
Language	English
Publishing date	2017-06-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2017.03.040
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Article ; Online: The Zebrafish, a Novel Model Organism for Screening Compounds Affecting Acute and Chronic Ethanol-Induced Effects.

Tran, S / Facciol, A / Gerlai, R

International review of neurobiology

2016 Volume 126, Page(s) 467–484

Abstract: Alcohol addiction is a major unmet medical and economic issue for which very few efficacious pharmacological treatment options are currently available. The development and identification of new compounds and drugs to treat alcohol addiction is hampered ... ...

Abstract	Alcohol addiction is a major unmet medical and economic issue for which very few efficacious pharmacological treatment options are currently available. The development and identification of new compounds and drugs to treat alcohol addiction is hampered by the high costs and low amenability of traditional laboratory rodents to high-throughput behavioral screens. The zebrafish represents an excellent compromise between systems complexity and practical simplicity by overcoming many limitations inherent in these rodent models. In this chapter, we review current advances in the behavioral and neurochemical characterization of ethanol-induced changes in zebrafish. We also discuss the basic principles and methods of and the most recent advances in using paradigms with which one can screen for compounds altering acute and chronic ethanol-induced effects in zebrafish.
MeSH term(s)	Alcoholism/drug therapy ; Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods ; Ethanol/adverse effects ; Zebrafish
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	209876-3
ISSN	2162-5514 ; 0074-7742
ISSN (online)	2162-5514
ISSN	0074-7742
DOI	10.1016/bs.irn.2016.02.016
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