ZENEREI Institute

Slidell, LA, United States

ZENEREI Institute

Slidell, LA, United States

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Kyzar E.J.,University of Illinois at Chicago | Kalueff A.V.,Guangdong Ocean University | Kalueff A.V.,ZENEREI Institute | Kalueff A.V.,Saint Petersburg State University
Zebrafish | Year: 2016

After decades of sociopolitical obstacles, the field of psychiatry is experiencing a revived interest in the use of hallucinogenic agents to treat brain disorders. Along with the use of ketamine for depression, recent pilot studies have highlighted the efficacy of classic serotonergic hallucinogens, such as lysergic acid diethylamide and psilocybin, in treating addiction, post-traumatic stress disorder, and anxiety. However, many basic pharmacological and toxicological questions remain unanswered with regard to these compounds. In this study, we discuss psychedelic medicine as well as the behavioral and toxicological effects of hallucinogenic drugs in zebrafish. We emphasize this aquatic organism as a model ideally suited to assess both the potential toxic and therapeutic effects of major known classes of hallucinogenic compounds. In addition, novel drugs with hallucinogenic properties can be efficiently screened using zebrafish models. Well-designed preclinical studies utilizing zebrafish can contribute to the reemerging treatment paradigm of psychedelic medicine, leading to new avenues of clinical exploration for psychiatric disorders. © Copyright 2016, Mary Ann Liebert, Inc. 2016.


Nguyen M.,University of Virginia | Nguyen M.,ZENEREI Institute | Roth A.,Texas Tech University Health Sciences Center | Kyzar E.J.,University of Illinois at Chicago | And 5 more authors.
Neurochemistry International | Year: 2014

Autism spectrum disorder (ASD) is a debilitating brain illness causing social deficits, delayed development and repetitive behaviors. ASD is a heritable neurodevelopmental disorder with poorly understood and complex etiology. The central dopaminergic system is strongly implicated in ASD pathogenesis. Genes encoding various elements of this system (including dopamine receptors, the dopamine transporter or enzymes of synthesis and catabolism) have been linked to ASD. Here, we comprehensively evaluate known molecular interactors of dopaminergic genes, and identify their potential molecular partners within up/down-steam signaling pathways associated with dopamine. These in silico analyses allowed us to construct a map of molecular pathways, regulated by dopamine and involved in ASD. Clustering these pathways reveals groups of genes associated with dopamine metabolism, encoding proteins that control dopamine neurotransmission, cytoskeletal processes, synaptic release, Ca2+ signaling, as well as the adenosine, glutamatergic and gamma-aminobutyric systems. Overall, our analyses emphasize the important role of the dopaminergic system in ASD, and implicate several cellular signaling processes in its pathogenesis. © 2014 Elsevier Ltd. All rights reserved.


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.,Tulane University | Roy S.,Tulane University | Wong K.,Tulane University | And 4 more authors.
Behavioural Brain Research | Year: 2015

Mounting clinical and experimental evidence implicates various cytokines in stress-related affective brain disorders. Here, we analyze behavioral phenotypes in C57BL/6J male mice following the chronic social defeat stress paradigm, and examine their serum cytokines and corticosterone levels. Loser mice experiencing 20 days of daily 15-min social confrontations demonstrate elevated levels of pro-inflammatory cytokines interleukin IL-7 and vascular endothelial growth factor (VEGF), as well as a trend to increase IL-6 and IL-15. We also found higher levels of an anti-inflammatory cytokine IL-10 in the winner mice, with unaltered serum IL-2, IL-4, IL-1a, MCP-1 and corticosterone levels between the groups. Overall, our results suggest that animal affective-like states correlate with specific cytokine profiles, including some cytokines (e.g., VEGF, IL-7 or IL-15) whose role in neuropsychiatric disorders is only beginning to emerge. This study emphasizes the importance of integrative analyses of neural and immune phenotypes in stress and stress-related neurobehavioral disorders. These findings may also help foster the search for new therapeutic and preventative strategies that target selected cytokines and their signaling pathways. © 2014 Elsevier B.V.


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.,ZENEREI Institute | Stewart A.M.,University of Pittsburgh | Cachat J.,ZENEREI Institute | Cachat J.,Tulane University | And 7 more authors.
Neurochemistry International | Year: 2013

Serotonin syndrome (SS) is a serious life-threatening disorder associated with elevated brain serotonergic function. With the growing use of serotonergic drugs, SS affects a large portion of general population, becoming a major biomedical concern. SS-like behaviors have also been reported in animals following administration of serotonergic drugs. Although clinical and rodent studies have provided significant insight into the etiology of SS, its exact mechanisms and risk factors remain poorly understood. The need to develop more efficient psychotropic drugs also requires extensive high-throughput screening of novel compounds using sensitive in-vivo tests. The use of zebrafish (Danio rerio) in neuroscience research is rapidly expanding due to their homology to humans, robust behavioral and physiological responses, genetic tractability, and low costs. Here we discuss the potential of zebrafish models to study SS-related phenotypes induced by selected serotonergic drugs. Overall, zebrafish exposed to serotonergic agents and their combinations exhibit a characteristic top dwelling (surfacing behavior) and hypolocomotion which may represent potential markers of SS-like states in zebrafish. This behavior in zebrafish models positively correlates with brain concentrations of serotonin, suggesting the developing utility of zebrafish (and other aquatic models) for studying SS. Future research is expected to foster high-throughput screening of drug interactions, and pharmacogenetics studies identifying zebrafish mutations implicated in pathological SS-like states. © 2013 Elsevier Ltd. All rights reserved.


Kyzar E.,ZENEREI Institute | Stewart A.M.,ZENEREI Institute | Stewart A.M.,University of Pittsburgh | Landsman S.,ZENEREI Institute | And 6 more authors.
Brain Research | Year: 2013

Brain monoamines play a key role in the regulation of behavior. Reserpine depletes monoamines, and causes depression and hypoactivity in humans and rodents. In contrast, d-amphetamine increases brain monoamines' levels, and evokes hyperactivity and anxiety. However, the effects of these agents on behavior and in relation to monoamine levels remain poorly understood, necessitating further experimental studies to understand their psychotropic action. Zebrafish (Danio rerio) are rapidly emerging as a promising model organism for drug screening and translational neuroscience research. Here, we have examined the acute and long-term effects of reserpine and d-amphetamine on zebrafish behavior in the novel tank test. Overall, d-amphetamine (5 and 10 mg/L) evokes anxiogenic-like effects in zebrafish acutely, but not 7 days later. In contrast, reserpine (20 and 40 mg/L) did not evoke overt acute behavioral effects, but markedly reduced activity 7 days later, resembling motor retardation observed in depression and/or Parkinson's disease. Three-dimensional 'temporal' (X, Y, time) reconstructions of zebrafish locomotion further supports these findings, confirming the utility of 3D-based video-tracking analyses in zebrafish models of drug action. Our results show that zebrafish are highly sensitive to drugs bi-directionally modulating brain monoamines, generally paralleling rodent and clinical findings. Collectively, this emphasizes the potential of zebrafish tests to model complex brain disorders associated with monoamine dysregulation. © 2013 Elsevier B.V. All rights reserved.


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.


Neelkantan N.,ZENEREI Institute | Neelkantan N.,American International College | Mikhaylova A.,ZENEREI Institute | Mikhaylova A.,American International College | And 9 more authors.
ACS Chemical Neuroscience | Year: 2013

Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs' action. The utility of zebrafish (Danio rerio) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Possessing a fully characterized genome, both adult and larval zebrafish are currently widely used for in vivo screening of various psychotropic compounds, including hallucinogens and related drugs. Recognizing the growing importance of hallucinogens in biological psychiatry, here we discuss hallucinogenic-induced phenotypes in zebrafish and evaluate their potential as efficient preclinical models of drug-induced states in humans. © 2013 American Chemical Society.

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