PREFACE: What Do You Mean by “Translational Research”? An Enquiry Through Animal and Translational Models for CNS Drug Discovery: Psychiatric Disorders

McArthur, Robert A.; Borsini, Franco

doi:10.1016/b978-0-12-373861-5.00032-1

Cited by 10 publications

(11 citation statements)

References 243 publications

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“…Animal models attempt to parallel the human condition and many of these models have provided important information about mediating factors for medical and psychiatric disorders (c.f., Adan and Kaye, 2011; Buccafusco, 2001; Conn, 2008; Griffin, 2002; Kalueff, 2006; Kobeissy, 2012; McArthur and Borsini, 2008a,b,c; McKinney, 1988, 2001; Pankevich et al, 2013; Siegel, 2005; Verma and Singh, 2014; Warnick and Kalueff, 2010), including dual-diagnosis (Edwards and Koob, 2012). Particularly germane to the present topic, animal models have led to important findings on neural substrates mediating addiction to multiple substances of abuse (c.f., Bell and Rahman, 2016; De Biasi, 2015; Dwoskin, 2014; Ekhtiari and Paulus, 2016a, 2016b; Frascella et al, 2011; Heidbreder, 2008; Koob et al, 2014a; McArthur and Borsini, 2008c; Nader, 2016; Olmstead, 2011) and ethanol in particular (Bell et al, 2005, 2006b, 2012, 2013, 2014, 2016; Ciccocioppo, 2013; Crabbe et al, 2013; Knapp and Breese, 2012; Maldonado-Devincci et al, 2012; McBride and Li, 1998; McBride et al, 2014b; Ramsden, 2015; Ryabinin, 2012).…”

Section: Background From An Animal Model Perspectivementioning

confidence: 99%

Rat animal models for screening medications to treat alcohol use disorders

et al. 2017

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The purpose of this review is to present animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence. The focus will be on rats and in particular selectively bred rats. Brief introductions discuss various aspects of the clinical picture, which provide characteristics of individuals with alcohol use disorders (AUDs) to model in animals. Following this, multiple selectively bred rat lines will be described and evaluated in the context of animal models used to screen medications to treat AUDs. Next, common behavioral tests for drug efficacy will be discussed particularly as they relate to stages in the addiction cycle. Tables highlighting studies that have tested the effects of compounds using the respective techniques are included. Wherever possible the Tables are organized chronologically in ascending order to describe changes in the focus of research on AUDs over time. In general, high ethanol-consuming selectively bred rats have been used to test a wide range of compounds. Older studies usually followed neurobiological findings in the selected lines that supported an association with a propensity for high ethanol intake. Most of these tests evaluated the compound's effects on the maintenance of ethanol drinking. Very few compounds have been tested during ethanol-seeking and/or relapse and fewer still have assessed their effects during the acquisition of AUDs. Overall, while a substantial number of neurotransmitter and neuromodulatory system targets have been assessed; the roles of sex- and age-of-animal, as well as the acquisition of AUDs, ethanol-seeking and relapse continue to be factors and behaviors needing further study.

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Section: Background From An Animal Model Perspectivementioning

confidence: 99%

Rat animal models for screening medications to treat alcohol use disorders

et al. 2017

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“…Translational Neuroscience in mental health can be defined as basic science studies that are conducted with the specific intent to discover mechanisms, biomarkers, etiological factors or treatments for mental disorders, or clinical studies that provide a foundation for developing, or that directly test, novel therapeutic strategies for people suffering from mental disorders. (McArthur & Borsini, 2008). The emphasis here has to be on the terms “discover” and “novel”, which imply that in the strongest form of translational neuroscience, neuroscientific and other biological data should make a novel contribution, whereby findings from studies of neurobiological processes change what we do in the clinic (or community) - not just “biologizes” what we do anyway (as noted above).…”

Section: Framework For Translational Neurosciencementioning

confidence: 99%

Multi-Level Models of Internalizing Disorders and Translational Developmental Science: Seeking Etiological Insights that can Inform Early Intervention Strategies

Allen

Dahl

2015

J Abnorm Child Psychol

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This commentary discusses the articles in this special section with an emphasis on the specific utility of multivariate, multi-level models in developmental psychopathology for ultimately contributing to both etiologic insights and translational advances. These issues are considered not only in terms of the specific papers, but also within a larger set of questions regarding the opportunities (and challenges) currently facing the field. We describe why we believe this an exciting time for integrative team-science approaches to tackle these challenges—a time that holds great promise for rapid advances in integrative developmental science that includes a biological level of mechanistic understanding. In order to facilitate this, we outline a range of approaches within both translational neuroscience and translational developmental science that can be used as frameworks for understanding how such research can provide etiologic insights regarding real-world targets at the level of social, behavioral, and affective processes that can be modified during key developmental windows of opportunity. We conclude that a “construct validity” framework, where biological data form a critical, but not privileged, component of key etiological mechanisms, combined with a developmental perspective on key period of sensitivity to intervention effects, is most likely to provide significant translational outcomes.

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“…Endophenotypes, also referred to as intermediate phenotypes (Tan et al, 2008), are heritable, primarily state-independent markers seen in diseased individuals. Due to their heritability, endophenotypes are also observed more frequently in nondiseased family members of the patients than in the general population (Gottesman and Shields, 1973; Gould and Gottesman, 2006; McArthur and Borsini, 2008). Two examples of endophenotypes are prepulse inhibition and P50 deficits seen in schizophrenia patients and their relatives (Braff et al ., 2008; Javitt et al ., 2008; Geyer, 2006b; Patterson et al ., 2008).…”

Section: How Animal Models Can Contribute Effectively To Drug Discovementioning

confidence: 99%

“…Discussions have addressed the possibility that this phenomenon reflects the comorbidity of multiple diagnostic entities within individual patients versus substantial overlaps in the symptoms that characterize various diagnostic syndromes (Geyer, 2006b; Markou et al ., 1998; Gould and Gottesman, 2006; McArthur and Borsini, 2008). Because the latter view appears to be most widely accepted (see references above), the development of the new American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-V) is taking a far more dimensional approach than ever before (Lecrubier, 2008).…”

Section: How Animal Models Can Contribute Effectively To Drug Discovementioning

confidence: 99%

Removing Obstacles in Neuroscience Drug Discovery: The Future Path for Animal Models

Markou

Chiamulera

Geyer

et al. 2008

Neuropsychopharmacol

296

249

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Despite great advances in basic neuroscience knowledge, the improved understanding of brain functioning has not yet led to the introduction of truly novel pharmacological approaches to the treatment of central nervous system disorders. This situation has been partly attributed to the difficulty of predicting efficacy in patients based on results from preclinical studies. To address these issues, this review critically discusses the traditional role of animal models in drug discovery, the difficulties encountered, and the reasons why this approach has led to suboptimal utilization of the information animal models provide. The discussion focuses on how animal models can contribute most effectively to translational medicine and drug discovery and the changes needed to increase the probability of achieving clinical benefit. Emphasis is placed on the need to improve the flow of information from the clinical/human domain to the preclinical domain and the benefits of using truly translational measures in both preclinical and clinical testing. Few would dispute the need to move away from the concept of modeling CNS diseases in their entirety using animals. However, the current emphasis on specific dimensions of psychopathology that can be objectively assessed in both clinical populations and animal models has not yet provided concrete examples of successful preclinical-clinical translation in CNS drug discovery. The purpose of this review is to strongly encourage ever more intensive clinical and preclinical interactions to ensure that basic science knowledge gained from improved animal models with good predictive and construct validity readily becomes available to the pharmaceutical industry and clinical researchers to benefit patients as quickly as possible.

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PREFACE: What Do You Mean by “Translational Research”? An Enquiry Through Animal and Translational Models for CNS Drug Discovery: Psychiatric Disorders

Cited by 10 publications

References 243 publications

Rat animal models for screening medications to treat alcohol use disorders

Rat animal models for screening medications to treat alcohol use disorders

Multi-Level Models of Internalizing Disorders and Translational Developmental Science: Seeking Etiological Insights that can Inform Early Intervention Strategies

Removing Obstacles in Neuroscience Drug Discovery: The Future Path for Animal Models

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