Peter Canavello - Academia.edu (original) (raw)

Papers by Peter Canavello

Research paper thumbnail of Genetic Animal Models of Depression

Humana Press eBooks, Nov 3, 2009

ABSTRACT

Research paper thumbnail of GABA – γ-amino butyric acid MGI – Mouse Genome Informatics Database MPD – Mouse Phenome Database

Research paper thumbnail of Chapter 11 Measuring Endocrine (Cortisol) Responses of Zebrafish to Stress

The zebrafish (Danio rerio) is rapidly becoming a popular model species in stress and neuroscienc... more The zebrafish (Danio rerio) is rapidly becoming a popular model species in stress and neuroscience research. Their behavior, robustly affected by environmental and pharmacological manipulations, can be paralleled by physiological (endocrine) analysis. Zebrafish have a hypothalamic-pituitary-interrenal (HPI) axis, which is homologous to the human hypothalamic-pituitary-adrenal (HPA) axis. While mice and rats use corticosterone as their main stress hormone, both humans and zebrafish utilize cortisol. This protocol explains the whole-body cortisol extraction procedure and the use of the human salivary cortisol ELISA kit to measure the amount of cortisol in each zebrafish sample. The ability to correlate physiological data from individual fish with behavioral data provides researchers with a valuable tool for investigating stress and anxiety, and contributes to the utility of zebrafish neurobehavioral models of stress.

Research paper thumbnail of Modeling Stress and Anxiety in Zebrafish

Neuromethods, 2010

While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, t... more While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, they also possess several qualities that make them particularly useful for studying stress and anxiety-related behaviors. Zebrafish neuroendocrine responses are robust, and correlate strongly with behavioral endpoints. These fish are also highly sensitive to various environmental challenges, including novelty stress, exposure to predators, alarm pheromone, anxiogenic drugs, and drug withdrawal. In addition, varying levels of baseline anxiety can be observed in different strains of zebrafish. Collectively, this supports the validity and efficacy of the adult zebrafish model for studying both acute and chronic anxiety.

Research paper thumbnail of Chapter 1 Video-Aided Analysis of Zebrafish Locomotion and Anxiety-Related Behavioral Responses

Due to physiological and anatomical similarities to other vertebrates, zebrafish are becoming a w... more Due to physiological and anatomical similarities to other vertebrates, zebrafish are becoming a widely used model in neurobehavioral research. With the growing popularity of zebrafish as experimental sub-jects, it is important to develop tools that accurately record their behavioral phenotypes. Video-aided analysis of zebrafish behavior offers an increased spectrum of behavioral endpoints, some of which are not available using traditional (manual) observation. In addition, the use of computer software allows quantification of certain zebrafish behaviors that are otherwise highly subjective. This protocol describes a method for fast, accurate, and consistent video-aided measurements of zebrafish locomotion and anxiety-related behavior.

Research paper thumbnail of Mutant and transgenic zebrafish in modeling neurobehavioral disorders

Zebrafish have traditionally been used as effective genetic and developmental models in biomedica... more Zebrafish have traditionally been used as effective genetic and developmental models in biomedical research. Recently, the scope and utility of zebrafish in biomedical research has been further expanded with the implementation of new genetic techniques aimed at developing translational models of human pathogenesis. Additionally, screens measuring specific neurobehavioral and developmental phenotypes have proven to be very robust. This chapter further discusses the utility of zebrafish in biomedical research and highlights some of the genetic techniques used in the creation of transgenic and mutant strains. Behavioral phenotypes of genetically altered zebrafish are also discussed with respect to both their robust stress responses and similarity to human disorders. Specific emphasis is placed on human brain pathogen-esis and neurodevelopmental abnormalities, especially as they relate to stress and anxiety spectrum disorders. Key words: Zebrafish, Genetics, Translational models Biomedi...

Research paper thumbnail of Chapter 10 Genetic Animal Models of Depression

Depression, as part of a larger class of affective disorders, is one of the world’s most deleteri... more Depression, as part of a larger class of affective disorders, is one of the world’s most deleterious and widespread neurobehavioral diseases. However, much remains to be discovered concerning depression, due to the daunting complexity of its pathological mechanisms and etiology. Various animal models have been proposed over the years, some of which have come into widespread use, particularly in the area of pharmacological screening. By combining behavioral and physiological analyses with mutant and trans-genic animal models, researchers are able to determine the role of specific genes and proteins in the pathogenesis of depression. Discussing several behavioral and transgenic/mutant rodent models, this chapter briefly summarizes the current progress in this area of psychiatric research.

Research paper thumbnail of Chapter 3 Modeling Stress and Anxiety in Zebrafish

While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, t... more While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, they also possess several qualities that make them particularly useful for studying stress and anxiety-related behav-iors. Zebrafish neuroendocrine responses are robust, and correlate strongly with behavioral endpoints. These fish are also highly sensitive to various environmental challenges, including novelty stress, exposure to predators, alarm pheromone, anxiogenic drugs, and drug withdrawal. In addition, varying levels of baseline anxiety can be observed in different strains of zebrafish. Collectively, this supports the validity and efficacy of the adult zebrafish model for studying both acute and chronic anxiety.

Research paper thumbnail of Mutant and Transgenic Zebrafish in Modeling Neurobehavioral Disorders

Zebrafish have traditionally been used as effective genetic and developmental models in biomedica... more Zebrafish have traditionally been used as effective genetic and developmental models in biomedical research. Recently, the scope and utility of zebrafish in biomedical research has been further expanded with the implementation of new genetic techniques aimed at developing translational models of human pathogenesis. Additionally, screens measuring specific neurobehavioral and developmental phenotypes have proven to be very robust. This chapter further discusses the utility of zebrafish in biomedical research and highlights some of the genetic techniques used in the creation of transgenic and mutant strains. Behavioral phenotypes of genetically altered zebrafish are also discussed with respect to both their robust stress responses and similarity to human disorders. Specific emphasis is placed on human brain pathogenesis and neurodevelopmental abnormalities, especially as they relate to stress and anxiety spectrum disorders.

Research paper thumbnail of Modeling Stress and Anxiety in Zebrafish

Neuromethods, 2010

While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, t... more While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, they also possess several qualities that make them particularly useful for studying stress and anxiety-related behaviors. Zebrafish neuroendocrine responses are robust, and correlate strongly with behavioral endpoints. These fish are also highly sensitive to various environmental challenges, including novelty stress, exposure to predators, alarm pheromone, anxiogenic drugs, and drug withdrawal. In addition, varying levels of baseline anxiety can be observed in different strains of zebrafish. Collectively, this supports the validity and efficacy of the adult zebrafish model for studying both acute and chronic anxiety.

Research paper thumbnail of Genetic Animal Models of Depression

Depression, as part of a larger class of affective disorders, is one of the world's most deleteri... more Depression, as part of a larger class of affective disorders, is one of the world's most deleterious and widespread neurobehavioral diseases. However, much remains to be discovered concerning depression, due to the daunting complexity of its pathological mechanisms and etiology. Various animal models have been proposed over the years, some of which have come into widespread use, particularly in the area of pharmacological screening. By combining behavioral and physiological analyses with mutant and transgenic animal models, researchers are able to determine the role of specific genes and proteins in the pathogenesis of depression. Discussing several behavioral and transgenic/mutant rodent models, this chapter briefly summarizes the current progress in this area of psychiatric research.

Research paper thumbnail of Behavioral phenotyping of mouse grooming and barbering

Usually more frequent in the home cage (Berridge et al., 2005), self-grooming is also seen in str... more Usually more frequent in the home cage (Berridge et al., 2005), self-grooming is also seen in stressful situations, such as novelty-based anxiety tests (e.g., elevated plus maze, open field and holeboard tests), implying that this behavior is not only important to assess, but can also interfere with the primary behavior being assessed, thus becoming a confounding factor, if neglected. Nevertheless, in many studies this behavior has received little attention. Surprisingly, there is no grooming data in the extensive Mouse Phenome Database (MPD), nor in recent comprehensive studies (Rogers et al., 1999; Tang et al., 2002; Voikar et al., 2001, 2004). Some authors assessed several grooming patterns but reported only one global behavioral score (e.g., Dunn et al., 1987). Others compared different strains but analyzed only cumulative scores (Cabib and Bonaventura, 1997; Nyberg et al., 2003; Leppanen et al., 2006), or even combined grooming data in-overall activity scores‖ with horizontal and vertical exploration (e.g., Wirth-Dzieciolowska et al., 2005). Still other studies assessed grooming indices in different strains cursorily among other measures, mostly including gross activity characteristics such as the latency, frequency and duration of grooming (e.g.

Research paper thumbnail of Prognostic significance of cytoplasmic SOX9 in invasive ductal carcinoma and metastatic breast cancer

Experimental biology and medicine (Maywood, N.J.), 2011

SOX9, a high mobility group (HMG) box transcription factor, is required for development, differen... more SOX9, a high mobility group (HMG) box transcription factor, is required for development, differentiation and lineage commitment. It is known to exert its effects through nuclear translocation, such as cell cycle changes in response to retinoic acid treatment in breast cancer cells. However, it is not known whether SOX9 has prognostic significance in human breast cancer. Over-expression and cytoplasmic sequestration of nuclear proteins are implicated in tumor progression. To determine whether SOX9 has any prognostic significance in human breast cancer, its expression and subcellular localization were analyzed in more than 200 human breast carcinomas (BCs). SOX9 mRNA expression data for human BCs were computed from microarray studies available in public databases and correlated with known poor prognostic parameters of BCs. SOX9 protein expression and its correlation with Ki-67 staining in human BCs were assessed using immunohistochemistry. Higher SOX9 mRNA levels were significantly as...

Research paper thumbnail of Measuring endocrine (cortisol) responses of zebrafish to stress

Neuromethods, 2011

The zebrafish (Danio rerio) is rapidly becoming a popular model species in stress and neuroscienc... more The zebrafish (Danio rerio) is rapidly becoming a popular model species in stress and neuroscience research. Their behavior, robustly affected by environmental and pharmacological manipulations, can be paralleled by physiological (endocrine) analysis. Zebrafish have a hypothalamic-pituitary-interrenal (HPI) axis, which is homologous to the human hypothalamic-pituitary-adrenal (HPA) axis. While mice and rats use corticosterone as their main stress hormone, both humans and zebrafish utilize cortisol. This protocol explains the whole-body cortisol extraction procedure and the use of the human salivary cortisol ELISA kit to measure the amount of cortisol in each zebrafish sample. The ability to correlate physiological data from individual fish with behavioral data provides researchers with a valuable tool for investigating stress and anxiety, and contributes to the utility of zebrafish neurobehavioral models of stress.

Research paper thumbnail of Video-Aided Analysis of Zebrafish Locomotion and Anxiety-Related Behavioral Responses

Neuromethods, 2010

Due to physiological and anatomical similarities to other vertebrates, zebrafish are becoming a w... more Due to physiological and anatomical similarities to other vertebrates, zebrafish are becoming a widely used model in neurobehavioral research. With the growing popularity of zebrafish as experimental subjects, it is important to develop tools that accurately record their behavioral phenotypes. Video-aided analysis of zebrafish behavior offers an increased spectrum of behavioral endpoints, some of which are not available using traditional (manual) observation. In addition, the use of computer software allows quantification of certain zebrafish behaviors that are otherwise highly subjective. This protocol describes a method for fast, accurate, and consistent video-aided measurements of zebrafish locomotion and anxietyrelated behavior.

Research paper thumbnail of Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish

Behavioural Brain Research, 2009

The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of... more The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and highthroughput model of stress and affective disorders.

Research paper thumbnail of Modeling withdrawal syndrome in zebrafish

Behavioural brain research, Apr 2, 2010

The zebrafish (Danio rerio) is rapidly becoming a popular model species in behavioral neuroscienc... more The zebrafish (Danio rerio) is rapidly becoming a popular model species in behavioral neuroscience research. Zebrafish behavior is robustly affected by environmental and pharmacological manipulations, and can be examined using exploration-based paradigms, paralleled by analysis of endocrine (cortisol) stress responses. Discontinuation of various psychotropic drugs evokes withdrawal in both humans and rodents, characterized by increased anxiety. Sensitivity of zebrafish to drugs of abuse has been recently reported in ...

Research paper thumbnail of Qui non proficit, deficit: Experimental models for ‘integrative’ research of affective disorders

Experimental models are an important tool for the study of biological mechanisms of psychiatric d... more Experimental models are an important tool for the study of biological mechanisms of psychiatric disorders. Although encouraging progress has been made in biological psychiatry of affective disorders, there remain numerous methodological, conceptual, and translational challenges in this field. Mounting clinical data support the view that psychiatric disorders as spectra, rather than as discrete or isolated illnesses. This requires new theories as well as new animal paradigms for "integrative" modeling of psychiatric disorders and their spectra. Here we discuss recent "integrative" experimental models and concepts that promise to advance translational research of affective disorders.

Research paper thumbnail of Genetic Animal Models of Depression

Humana Press eBooks, Nov 3, 2009

ABSTRACT

Research paper thumbnail of GABA – γ-amino butyric acid MGI – Mouse Genome Informatics Database MPD – Mouse Phenome Database

Research paper thumbnail of Chapter 11 Measuring Endocrine (Cortisol) Responses of Zebrafish to Stress

The zebrafish (Danio rerio) is rapidly becoming a popular model species in stress and neuroscienc... more The zebrafish (Danio rerio) is rapidly becoming a popular model species in stress and neuroscience research. Their behavior, robustly affected by environmental and pharmacological manipulations, can be paralleled by physiological (endocrine) analysis. Zebrafish have a hypothalamic-pituitary-interrenal (HPI) axis, which is homologous to the human hypothalamic-pituitary-adrenal (HPA) axis. While mice and rats use corticosterone as their main stress hormone, both humans and zebrafish utilize cortisol. This protocol explains the whole-body cortisol extraction procedure and the use of the human salivary cortisol ELISA kit to measure the amount of cortisol in each zebrafish sample. The ability to correlate physiological data from individual fish with behavioral data provides researchers with a valuable tool for investigating stress and anxiety, and contributes to the utility of zebrafish neurobehavioral models of stress.

Research paper thumbnail of Modeling Stress and Anxiety in Zebrafish

Neuromethods, 2010

While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, t... more While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, they also possess several qualities that make them particularly useful for studying stress and anxiety-related behaviors. Zebrafish neuroendocrine responses are robust, and correlate strongly with behavioral endpoints. These fish are also highly sensitive to various environmental challenges, including novelty stress, exposure to predators, alarm pheromone, anxiogenic drugs, and drug withdrawal. In addition, varying levels of baseline anxiety can be observed in different strains of zebrafish. Collectively, this supports the validity and efficacy of the adult zebrafish model for studying both acute and chronic anxiety.

Research paper thumbnail of Chapter 1 Video-Aided Analysis of Zebrafish Locomotion and Anxiety-Related Behavioral Responses

Due to physiological and anatomical similarities to other vertebrates, zebrafish are becoming a w... more Due to physiological and anatomical similarities to other vertebrates, zebrafish are becoming a widely used model in neurobehavioral research. With the growing popularity of zebrafish as experimental sub-jects, it is important to develop tools that accurately record their behavioral phenotypes. Video-aided analysis of zebrafish behavior offers an increased spectrum of behavioral endpoints, some of which are not available using traditional (manual) observation. In addition, the use of computer software allows quantification of certain zebrafish behaviors that are otherwise highly subjective. This protocol describes a method for fast, accurate, and consistent video-aided measurements of zebrafish locomotion and anxiety-related behavior.

Research paper thumbnail of Mutant and transgenic zebrafish in modeling neurobehavioral disorders

Zebrafish have traditionally been used as effective genetic and developmental models in biomedica... more Zebrafish have traditionally been used as effective genetic and developmental models in biomedical research. Recently, the scope and utility of zebrafish in biomedical research has been further expanded with the implementation of new genetic techniques aimed at developing translational models of human pathogenesis. Additionally, screens measuring specific neurobehavioral and developmental phenotypes have proven to be very robust. This chapter further discusses the utility of zebrafish in biomedical research and highlights some of the genetic techniques used in the creation of transgenic and mutant strains. Behavioral phenotypes of genetically altered zebrafish are also discussed with respect to both their robust stress responses and similarity to human disorders. Specific emphasis is placed on human brain pathogen-esis and neurodevelopmental abnormalities, especially as they relate to stress and anxiety spectrum disorders. Key words: Zebrafish, Genetics, Translational models Biomedi...

Research paper thumbnail of Chapter 10 Genetic Animal Models of Depression

Depression, as part of a larger class of affective disorders, is one of the world’s most deleteri... more Depression, as part of a larger class of affective disorders, is one of the world’s most deleterious and widespread neurobehavioral diseases. However, much remains to be discovered concerning depression, due to the daunting complexity of its pathological mechanisms and etiology. Various animal models have been proposed over the years, some of which have come into widespread use, particularly in the area of pharmacological screening. By combining behavioral and physiological analyses with mutant and trans-genic animal models, researchers are able to determine the role of specific genes and proteins in the pathogenesis of depression. Discussing several behavioral and transgenic/mutant rodent models, this chapter briefly summarizes the current progress in this area of psychiatric research.

Research paper thumbnail of Chapter 3 Modeling Stress and Anxiety in Zebrafish

While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, t... more While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, they also possess several qualities that make them particularly useful for studying stress and anxiety-related behav-iors. Zebrafish neuroendocrine responses are robust, and correlate strongly with behavioral endpoints. These fish are also highly sensitive to various environmental challenges, including novelty stress, exposure to predators, alarm pheromone, anxiogenic drugs, and drug withdrawal. In addition, varying levels of baseline anxiety can be observed in different strains of zebrafish. Collectively, this supports the validity and efficacy of the adult zebrafish model for studying both acute and chronic anxiety.

Research paper thumbnail of Mutant and Transgenic Zebrafish in Modeling Neurobehavioral Disorders

Zebrafish have traditionally been used as effective genetic and developmental models in biomedica... more Zebrafish have traditionally been used as effective genetic and developmental models in biomedical research. Recently, the scope and utility of zebrafish in biomedical research has been further expanded with the implementation of new genetic techniques aimed at developing translational models of human pathogenesis. Additionally, screens measuring specific neurobehavioral and developmental phenotypes have proven to be very robust. This chapter further discusses the utility of zebrafish in biomedical research and highlights some of the genetic techniques used in the creation of transgenic and mutant strains. Behavioral phenotypes of genetically altered zebrafish are also discussed with respect to both their robust stress responses and similarity to human disorders. Specific emphasis is placed on human brain pathogenesis and neurodevelopmental abnormalities, especially as they relate to stress and anxiety spectrum disorders.

Research paper thumbnail of Modeling Stress and Anxiety in Zebrafish

Neuromethods, 2010

While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, t... more While zebrafish (Danio rerio) are widely utilized as a model species for neuroscience research, they also possess several qualities that make them particularly useful for studying stress and anxiety-related behaviors. Zebrafish neuroendocrine responses are robust, and correlate strongly with behavioral endpoints. These fish are also highly sensitive to various environmental challenges, including novelty stress, exposure to predators, alarm pheromone, anxiogenic drugs, and drug withdrawal. In addition, varying levels of baseline anxiety can be observed in different strains of zebrafish. Collectively, this supports the validity and efficacy of the adult zebrafish model for studying both acute and chronic anxiety.

Research paper thumbnail of Genetic Animal Models of Depression

Depression, as part of a larger class of affective disorders, is one of the world's most deleteri... more Depression, as part of a larger class of affective disorders, is one of the world's most deleterious and widespread neurobehavioral diseases. However, much remains to be discovered concerning depression, due to the daunting complexity of its pathological mechanisms and etiology. Various animal models have been proposed over the years, some of which have come into widespread use, particularly in the area of pharmacological screening. By combining behavioral and physiological analyses with mutant and transgenic animal models, researchers are able to determine the role of specific genes and proteins in the pathogenesis of depression. Discussing several behavioral and transgenic/mutant rodent models, this chapter briefly summarizes the current progress in this area of psychiatric research.

Research paper thumbnail of Behavioral phenotyping of mouse grooming and barbering

Usually more frequent in the home cage (Berridge et al., 2005), self-grooming is also seen in str... more Usually more frequent in the home cage (Berridge et al., 2005), self-grooming is also seen in stressful situations, such as novelty-based anxiety tests (e.g., elevated plus maze, open field and holeboard tests), implying that this behavior is not only important to assess, but can also interfere with the primary behavior being assessed, thus becoming a confounding factor, if neglected. Nevertheless, in many studies this behavior has received little attention. Surprisingly, there is no grooming data in the extensive Mouse Phenome Database (MPD), nor in recent comprehensive studies (Rogers et al., 1999; Tang et al., 2002; Voikar et al., 2001, 2004). Some authors assessed several grooming patterns but reported only one global behavioral score (e.g., Dunn et al., 1987). Others compared different strains but analyzed only cumulative scores (Cabib and Bonaventura, 1997; Nyberg et al., 2003; Leppanen et al., 2006), or even combined grooming data in-overall activity scores‖ with horizontal and vertical exploration (e.g., Wirth-Dzieciolowska et al., 2005). Still other studies assessed grooming indices in different strains cursorily among other measures, mostly including gross activity characteristics such as the latency, frequency and duration of grooming (e.g.

Research paper thumbnail of Prognostic significance of cytoplasmic SOX9 in invasive ductal carcinoma and metastatic breast cancer

Experimental biology and medicine (Maywood, N.J.), 2011

SOX9, a high mobility group (HMG) box transcription factor, is required for development, differen... more SOX9, a high mobility group (HMG) box transcription factor, is required for development, differentiation and lineage commitment. It is known to exert its effects through nuclear translocation, such as cell cycle changes in response to retinoic acid treatment in breast cancer cells. However, it is not known whether SOX9 has prognostic significance in human breast cancer. Over-expression and cytoplasmic sequestration of nuclear proteins are implicated in tumor progression. To determine whether SOX9 has any prognostic significance in human breast cancer, its expression and subcellular localization were analyzed in more than 200 human breast carcinomas (BCs). SOX9 mRNA expression data for human BCs were computed from microarray studies available in public databases and correlated with known poor prognostic parameters of BCs. SOX9 protein expression and its correlation with Ki-67 staining in human BCs were assessed using immunohistochemistry. Higher SOX9 mRNA levels were significantly as...

Research paper thumbnail of Measuring endocrine (cortisol) responses of zebrafish to stress

Neuromethods, 2011

The zebrafish (Danio rerio) is rapidly becoming a popular model species in stress and neuroscienc... more The zebrafish (Danio rerio) is rapidly becoming a popular model species in stress and neuroscience research. Their behavior, robustly affected by environmental and pharmacological manipulations, can be paralleled by physiological (endocrine) analysis. Zebrafish have a hypothalamic-pituitary-interrenal (HPI) axis, which is homologous to the human hypothalamic-pituitary-adrenal (HPA) axis. While mice and rats use corticosterone as their main stress hormone, both humans and zebrafish utilize cortisol. This protocol explains the whole-body cortisol extraction procedure and the use of the human salivary cortisol ELISA kit to measure the amount of cortisol in each zebrafish sample. The ability to correlate physiological data from individual fish with behavioral data provides researchers with a valuable tool for investigating stress and anxiety, and contributes to the utility of zebrafish neurobehavioral models of stress.

Research paper thumbnail of Video-Aided Analysis of Zebrafish Locomotion and Anxiety-Related Behavioral Responses

Neuromethods, 2010

Due to physiological and anatomical similarities to other vertebrates, zebrafish are becoming a w... more Due to physiological and anatomical similarities to other vertebrates, zebrafish are becoming a widely used model in neurobehavioral research. With the growing popularity of zebrafish as experimental subjects, it is important to develop tools that accurately record their behavioral phenotypes. Video-aided analysis of zebrafish behavior offers an increased spectrum of behavioral endpoints, some of which are not available using traditional (manual) observation. In addition, the use of computer software allows quantification of certain zebrafish behaviors that are otherwise highly subjective. This protocol describes a method for fast, accurate, and consistent video-aided measurements of zebrafish locomotion and anxietyrelated behavior.

Research paper thumbnail of Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish

Behavioural Brain Research, 2009

The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of... more The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and highthroughput model of stress and affective disorders.

Research paper thumbnail of Modeling withdrawal syndrome in zebrafish

Behavioural brain research, Apr 2, 2010

The zebrafish (Danio rerio) is rapidly becoming a popular model species in behavioral neuroscienc... more The zebrafish (Danio rerio) is rapidly becoming a popular model species in behavioral neuroscience research. Zebrafish behavior is robustly affected by environmental and pharmacological manipulations, and can be examined using exploration-based paradigms, paralleled by analysis of endocrine (cortisol) stress responses. Discontinuation of various psychotropic drugs evokes withdrawal in both humans and rodents, characterized by increased anxiety. Sensitivity of zebrafish to drugs of abuse has been recently reported in ...

Research paper thumbnail of Qui non proficit, deficit: Experimental models for ‘integrative’ research of affective disorders

Experimental models are an important tool for the study of biological mechanisms of psychiatric d... more Experimental models are an important tool for the study of biological mechanisms of psychiatric disorders. Although encouraging progress has been made in biological psychiatry of affective disorders, there remain numerous methodological, conceptual, and translational challenges in this field. Mounting clinical data support the view that psychiatric disorders as spectra, rather than as discrete or isolated illnesses. This requires new theories as well as new animal paradigms for "integrative" modeling of psychiatric disorders and their spectra. Here we discuss recent "integrative" experimental models and concepts that promise to advance translational research of affective disorders.