ZENEREI Institute

Slidell, LA, United States

ZENEREI Institute

Slidell, LA, United States
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Kyzar E.J.,University of Illinois at Chicago | Stewart A.M.,ZENEREI Institute | Kalueff A.V.,ZENEREI Institute | Kalueff A.V.,Guangdong Ocean University | Kalueff A.V.,Saint Petersburg State University
Behavioural Brain Research | Year: 2016

Serotonin (5-HT) plays a crucial role in the brain, modulating mood, cognition and reward. The serotonin transporter (SERT) is responsible for the reuptake of 5-HT from the synaptic cleft and regulates serotonin signaling in the brain. In humans, SERT genetic variance is linked to the pathogenesis of various psychiatric disorders, including anxiety, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Rodent self-grooming is a complex, evolutionarily conserved patterned behavior relevant to stress, ASD and OCD. Genetic ablation of mouse Sert causes various behavioral deficits, including increased anxiety and grooming behavior. The hallucinogenic drug lysergic acid diethylamide (LSD) is a potent serotonergic agonist known to modulate human and animal behavior. Here, we examined heterozygous Sert+/- mouse behavior following acute administration of LSD (0.32mg/kg). Overall, Sert+/- mice displayed a longer duration of self-grooming behavior regardless of LSD treatment. In contrast, LSD increased serotonin-sensitive behaviors, such as head twitching, tremors and backwards gait behaviors in both Sert+/+ and Sert+/- mice. There were no significant interactions between LSD treatment and Sert gene dosage in any of the behavioral domains measured. These results suggest that Sert+/- mice may respond to the behavioral effects of LSD in a similar manner to wild-type mice. © 2015 Elsevier B.V.


Kalueff A.V.,ZENEREI Institute | Stewart A.M.,ZENEREI Institute | Stewart A.M.,University of Pittsburgh | Gerlai R.,University of Toronto
Trends in Pharmacological Sciences | Year: 2014

The zebrafish (Danio rerio) is rapidly becoming a popular model organism in pharmacogenetics and neuropharmacology. Both larval and adult zebrafish are currently used to increase our understanding of brain function, dysfunction, and their genetic and pharmacological modulation. Here we review the developing utility of zebrafish in the analysis of complex brain disorders (including, e.g., depression, autism, psychoses, drug abuse, and cognitive deficits), also covering zebrafish applications towards the goal of modeling major human neuropsychiatric and drug-induced syndromes. We argue that zebrafish models of complex brain disorders and drug-induced conditions are a rapidly emerging critical field in translational neuroscience and pharmacology research. © 2013 Elsevier Ltd. All rights reserved.


Stewart A.M.,ZENEREI Institute | Gerlai R.,University of Toronto | Kalueff A.V.,ZENEREI Institute | Kalueff A.V.,Guangdong Ocean University
Frontiers in Behavioral Neuroscience | Year: 2015

The high prevalence of brain disorders and the lack of their efficient treatments necessitate improved in-vivo pre-clinical models and tests. The zebrafish (Danio rerio), a vertebrate species with high genetic and physiological homology to humans, is an excellent organism for innovative central nervous system (CNS) drug discovery and small molecule screening. Here, we outline new strategies for developing higher-throughput zebrafish screens to test neuroactive drugs and predict their pharmacological mechanisms. With the growing application of automated 3D phenotyping, machine learning algorithms, movement pattern- and behavior recognition, and multi-animal video-tracking, zebrafish screens are expected to markedly improve CNS drug discovery. © 2015 Stewart, Gerlai and Kalueff. This is an open-access article distributed under the terms of the Creative Commons Attribution License.


Stewart A.M.,ZENEREI Institute | Stewart A.M.,University of Pittsburgh | Kalueff A.V.,ZENEREI Institute
Expert Opinion on Drug Discovery | Year: 2014

Introduction: Contemporary biological psychiatry uses experimental (animal) models to increase our understanding of affective disorder pathogenesis. Despite the well-recognized spectrum nature of affective disorders, modern anxiolytic drug discovery mainly targets specific pathways and molecular determinants within a single phenotypic domain. However, greater understanding of the integrative mechanisms and pathogenesis is essential in order to develop new effective therapies. Areas covered: In this review, the authors emphasize the importance of a 'domain interplay-oriented' approach to experimental affective research. They also highlight the need to expand the scope of anxiolytic drug targets to better understand the pathogenesis of anxiety-spectrum disorders. Expert opinion: There is the potential to markedly improve the utility of animal models for affective disorders. First, the authors suggest that one such way would be by analyzing the systems of several domains and their interplay to better understand disease pathogenesis. Further, it could also be improved by expanding the range of model species and by extending the spectrum of anxiolytic drug targets; this would help to focus on emerging and unconventional systems to better develop new therapies. © 2014 Informa UK, Ltd.


Kalueff A.V.,Guangdong Ocean University | Kalueff A.V.,ZENEREI Institute | Stewart A.M.,ZENEREI Institute | Stewart A.M.,University of Pittsburgh | And 3 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2015

Contemporary biological psychiatry uses clinical and experimental (animal) models to increase our understanding of brain pathogenesis. Modeling psychiatric disorders is currently performed by targeting various key neurobehavioral clusters of phenotypic traits (domains), including affective, cognitive, social, motor and reward. Analyses of such domains and their 'smaller units' - individual endophenotypes - are critical for the study of complex brain disorders and their neural underpinnings. The spectrum nature of brain disorders and the importance of pathogenetic linkage among various disordered domains or endophenotypes have also been recognized as an important strategic direction of translational research. Here, we discuss cross-domain analyses of animal models, and focus on their value for mimicking the clinical overlap between disordered neurobehavioral domains in humans. Based on recent experimental evidence, we argue that understanding of brain pathogenesis requires modeling the clinically relevant inter-relationships between various individual endophenotypes (or their domains). © 2015 Elsevier Ltd.


Kalueff A.V.,ZENEREI Institute | Nguyen M.,University of Virginia
Journal of Pharmacological and Toxicological Methods | Year: 2014

C57BL/6J mice are one of the most commonly used mouse strains in biobehavioral and psychopharmacological research. Prone to variance due to multiple environmental factors, animal neurophenotyping studies rely on using proper experimental protocols, study designs and well-established models and tests. Choosing the dose range for anxiolytic or anxiogenic drugs is key for obtaining valid testing results and correct data interpretation. Here we emphasize the importance of accurate dose selection in rodent anxiety paradigms for concluding whether the mouse strain used is "sensitive" and therefore appropriate for studying anxiety in selected behavioral tests. We also provide further argument in support of using the C57BL/6J mouse strain for testing anxiolytic and anxiogenic compounds. © 2014 Elsevier Inc.


Nguyen M.,University of Virginia | Nguyen M.,ZENEREI Institute | Stewart A.M.,ZENEREI Institute | Stewart A.M.,International Zebrafish Neuroscience Research Consortium ZNRC | And 3 more authors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2014

Depression is a serious psychiatric condition affecting millions of patients worldwide. Unipolar depression is characterized by low mood, anhedonia, social withdrawal and other severely debilitating psychiatric symptoms. Bipolar disorder manifests in alternating depressed mood and 'hyperactive' manic/hypomanic states. Animal experimental models are an invaluable tool for research into the pathogenesis of bipolar/unipolar depression, and for the development of potential treatments. Due to their high throughput value, genetic tractability, low cost and quick reproductive cycle, zebrafish (Danio rerio) have emerged as a promising new model species for studying brain disorders. Here, we discuss the developing utility of zebrafish for studying depression disorders, and outline future areas of research in this field. We argue that zebrafish represent a useful model organism for studying depression and its behavioral, genetic and physiological mechanisms, as well as for anti-depressant drug discovery. © 2014 Elsevier Inc.


Stewart A.M.,ZENEREI Institute | Stewart A.M.,International Zebrafish Neuroscience Research Consortium ZNRC | Ullmann J.F.P.,International Zebrafish Neuroscience Research Consortium ZNRC | Ullmann J.F.P.,University of Queensland | And 8 more authors.
Molecular Psychiatry | Year: 2015

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research. © 2015 Macmillan Publishers Limited All rights reserved 1359-4184/15.


Stewart A.M.,ZENEREI Institute | Stewart A.M.,University of Pittsburgh | Kalueff A.V.,ZENEREI Institute | Kalueff A.V.,Tulane University
Brain Research | Year: 2014

The use of psychotropic drugs in clinical and translational brain research continues to grow, and the need for novel experimental models and screens is becoming widely recognized. Mounting evidence supports the utility of zebrafish (Danio rerio) for studying various pharmacological manipulations, as an alternative model complementing the existing rodent paradigms in this field. Here, we explore the effects of acute 20-min exposure to two commonly abused psychotropic compounds, Δ9-tetrahydrocannabinol (THC) and heroin, on adult zebrafish behavior in the novel tank test. Overall, THC administration (30 and 50 mg/L) produces an anxiogenic-like reduction of top swimming, paralleled with a slower, continuous bottom swimming. In contrast, heroin exposure (15 and 25 mg/L) evoked a hyperlocomotor response (with rapid bouts of bottom swimming and frequent 'bouncing' motions) without altering anxiety-sensitive top/bottom endpoints. The behavioral effects of these two compounds in zebrafish seem to parallel the respective rodent and human findings. Collectively, this emphasizes the growing significance of novel emerging aquatic models in translational drug abuse research and small molecule screening. © 2013 Elsevier B.V.


Stewart A.M.,University of Illinois at Chicago | Kalueff A.V.,Tulane University | Kalueff A.V.,ZENEREI Institute
Current Neuropharmacology | Year: 2012

Whereas cognitive impairment is a common symptom in multiple brain disorders, predictive and highthroughput animal models of cognition and behavior are becoming increasingly important in the field of translational neuroscience research. In particular, reliable models of the cognitive deficits characteristic of numerous neurobehavioral disorders such as Alzheimer's disease and schizophrenia have become a significant focus of investigation. While rodents have traditionally been used to study cognitive phenotypes, zebrafish (Danio rerio) are gaining popularity as an excellent model to complement current translational neuroscience research. Here we discuss recent advances in pharmacological and genetic approaches using zebrafish models to study cognitive impairments and to discover novel cognitive enhancers and neuroprotective mechanisms. © 2012 Bentham Science Publishers.

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