Jason E. Warnick

Propranolol and Its Potential Inhibition of Positive Post-Traumatic Growth

Henry et al. (2007), in their discussion of the pharmacological manipulation of memory, present a sensible rejoinder to the frequent fanciful hypotheticals of the President’s Council on Bioethics (2003). The authors were successful in portraying post-traumatic stress disorder (PTSD) as a condition serious enough to warrant research into novel prospective therapeutics. However, their promotion of a pharmacological prophylaxis for PTSD could be quixotic, and even potentially calamitous, due to the potential for obstructive effects to personal development. While the President’s Council on Bioethics does not elaborate on how traumatic events can lead to positive changes in one’s life, they do make the claim that:

Sex Differences in Working Memory

In two separate studies, sex differences in modal-specific elements of working memory were investigated by utilizing words and pictures as stimuli. Groups of men and women performed a free-recall task of words or pictures in which 20 items were presented concurrently and the number of correct items recalled was measured. Following stimulus presentation, half of the participants were presented a verbal-based distraction task. On the verbal working-memory task, performance of men and women was not significantly different in the no-distraction condition. However, in the distraction condition, womens recall was significantly lower than their performance in the no-distraction condition and mens performance in the distraction condition. These findings are consistent with previous research and point to sex differences in cognitive ability putatively resulting from functional neuroanatomical dissimilarities. On the visual working-memory task, women showed significantly greater recall than men. These findings are inconsistent with previous research and underscore the need for further research.

Zebrafish models in neuropsychopharmacology and CNS drug discovery

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.

Zebrafish models of autism spectrum disorder

ABSTRACT Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by motor, social and cognitive deficits that develop early during childhood. The pathogenesis of ASD is not well characterized and involves a multifaceted interaction between genetic, neurobiological and environmental factors. Animal (experimental) models possess evolutionarily conserved behaviors and molecular pathways that are highly relevant for studying ASD. The zebrafish (Danio rerio) is a relatively new animal model with promise for understanding the pathogenesis of complex brain disorders and discovering novel treatments. As a highly social and genetically tractable organism, zebrafish have recently been applied to model a variety of deficits relevant to ASD. Here, we discuss the developing utility of zebrafish models of ASD, as well as current behavioral, toxicological and genetic models of ASD, and future directions of research in this field.

Adult zebrafish in CNS disease modeling: a tank that's half-full, not half-empty, and still filling

The zebrafish (Danio rerio) is increasingly used in a broad array of biomedical studies, from cancer research to drug screening. Zebrafish also represent an emerging model organism for studying complex brain diseases. The number of zebrafish neuroscience studies is exponentially growing, significantly outpacing those conducted with rodents or other model organisms. Yet, there is still a substantial amount of resistance in adopting zebrafish as a first-choice model system. Studies of the repertoire of zebrafish neural and behavioral functions continue to reveal new opportunities for understanding the pathobiology of various CNS deficits. Although some of these models are well established in zebrafish, including models for anxiety, depression, and addiction, others are less recognized, for example, models of autism and obsessive-compulsive states. However, mounting data indicate that a wide spectrum of CNS diseases can be modeled in adult zebrafish. Here, we summarize recent findings using zebrafish CNS assays, discuss model limitations and the existing challenges, as well as outline future directions of research in this field.

The failure of anxiolytic therapies in early clinical trials: what needs to be done

Introduction: Anxiety spectrum disorders (ASDs) are highly prevalent psychiatric illnesses that affect millions of people worldwide. Strongly associated with stress, common ASDs include generalized anxiety disorder, panic, social anxiety, phobias and drug-abuse-related anxiety. In addition to ASDs, several other prevalent psychiatric illnesses represent trauma/stressor-related disorders, such as post-traumatic stress disorder and acute stress disorder. Anxiolytic drugs, commonly prescribed to treat ASDs and trauma/stressor-related disorders, form a highly heterogenous group, modulating multiple neurotransmitters and physiological mechanisms. However, overt individual differences in efficacy and the potential for serious side-effects (including addiction and drug interaction) indicate a need for further drug development. Yet, over the past 50 years, there has been relatively little progress in the development of novel anxiolytic medications, especially when promising candidate drugs often fail in early clinical trials. Areas covered: Herein, the authors present recommendations of the Task Force on Anxiolytic Drugs of the International Stress and Behavior Society on how to improve anxiolytic drug discovery. These recommendations cover a wide spectrum of aspects, ranging from methodological improvements to conceptual insights and innovation. Expert opinion: In order to improve the success of anxiolytic drugs in early clinical trials, the goals of preclinical trials may need to be adjusted from a clinical perspective and better synchronized with those of clinical studies. Indeed, it is important to realize that the strategic goals and approaches must be similar if we want to have a smoother transition between phases.

Assessing the Maximum Predictive Validity for Neuropharmacological Anxiety Screening Assays Using Zebrafish

The development of reliable pharmacological screening assays is an important task. However, it is based upon the ability of animal models, such as the zebrafish, to demonstrate predictive validity for a specific set of drug classes. A popular assay used for this purpose is the novel tank diving paradigm, where zebrafish behavior can easily be modulated by anxiolytic or anxiogenic drug exposure. However, predictive validity may fail to provide crucial information about the model, such as comparisons of drug efficacy and the effects of drugs on varying behavioral phenotypes. This deficit is accounted for by a novel measure termed the Maximum Predictive Value (MPV), which provides an estimate of how sensitive a particular model is when assessing its potential pharmacologically. Here we provide a protocol detailing how to employ this measure to validate behavioral endpoints in the novel tank test for use in pharmacological studies in zebrafish. Similar approaches can be used to examine drug efficacy in other zebrafish-based behavioral tests.

Introduction and Rationale for This Book

Warnick and Landis provide an overview of the major models of intercultural relations to serve as a foundation for the subsequent chapters in this text. The reader will gain a greater understanding of how the emerging field of cultural neuroscience can be applied to intercultural relations. Additionally, this chapter offers a brief guide to the book.