Zebrafish models in neuropsychopharmacology and CNS drug discovery

Abstract

Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets.

Evolution of Epileptiform Activity in Zebrafish by Statistical-Based Integration of Electrophysiology and 2-Photon Ca2+ Imaging

“…Since about one-third of patients show no significant improvement in current therapeutic treatments [2], there is a clear need for a better understanding of the disease and for more effective drugs. Zebrafish is an emerging model for the study of human neurological disorders, and for the identification of potential therapeutic targets [3,4]. Although the Central Nervous Systems (CNS) of mammalian and teleost display considerable neuroanatomical differences, several fundamental principles of brain development and function are evolutionarily well conserved [5], thus allowing to recapitulate in the fish many mechanisms and clinical features of brain disorders [6].…”

Zebrafish as a High-Throughput In Vivo Model for Testing the Bioactivity of Cannabinoids

“…The use of zebrafish in the field of neuroscience continues to increase and a number of recent reviews have highlighted both the strengths and weaknesses of using zebrafish to study neuroactive compounds and brain disorders [9][10][11][12][13][14][15]. The zebrafish brain has many analogous regions to those of higher vertebrates and the complexity of both juvenile and adult zebrafish brains has been well documented [16].…”

“…It has been demonstrated that zebrafish are sensitive to a large number of neurotropic drugs including: antipsychotics, mood stabilizers, anxiolytics, antidepressants, ethanol, hypnotics, stimulants, hallucinogens, antiepileptics, analgesics and cognitive enhancers [15,16]. In addition, both adult and larval zebrafish can be used to model numerous neural disorders including pain/nociception, anxiety, stress, PTSD, ADHD, Autism, epilepsy, learning & memory deficits, psychiatric disorders, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, schizophrenia, bi-polar disorder, addiction and brain cancer [6,9,11,[14][15][16][20][21][22][23][24][25]. This provides in vivo models with which to test not only the bioactivity of various neuroactive compounds, but also allows for the testing of their potential efficacy against numerous models of disease.…”

“…Many of the neuronal disease models developed using zebrafish are centered on the assessment of aberrant behavior in both larvae and adults, which each provide their own distinct advantages [9,11,15,16]. One of the major advantages of using larvae over adults stems from their reproducible patterns of behavior and potential to be screened in a high throughput fashion.…”

Parallelism of Chemicostructural Properties between Filgrastim Originator and Three of Its Biosimilar Drugs

“…Moreover, in order to provide information about their functional activity, we performed an innovative functional analysis by utilizing zebrafish embryo (Danio rerio), to compare the effect of the drugs on immune system cell activation. Recently, zebrafish has become a very interesting animal model in different fields, including pharmacology and toxicology [21][22][23][24][25][26][27][28]. Aside from small molecule discovery and screening, it is now used for complex biological drugs characterization, such as biosimilars [29,30].…”