Genetic Approaches to Modeling Anxiety in Animals

Jacobson, Laura; Cryan, John F.

doi:10.1007/7854_2009_31

Cited by 29 publications

(29 citation statements)

References 260 publications

(332 reference statements)

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“…However, this has brought with it its own logistical problems in terms of difficulty in combining blood collection for pharmacokineticpharmacodynamic studies or biomarker analysis. Moreover, the enormous interstrain difference in mouse behaviour across many anxiety tests both under baseline conditions and in response to pharmacological manipulation (Jacobson and Cryan, 2010) can make interpretation of data difficult. The question which invariably arises as to which mouse strain is most like human is not an easy question to try and answer.…”

Section: Animal Models and Tests Used In Assessing Anxiolytic Actionmentioning

confidence: 99%

“…Development of novel genetic animal models has proven invaluable not only in this regard, but in the dissection of neurobiological basis of anxiety behaviour and in indicating potential therapeutic avenues for treatment of anxiety disorders (Jacobson and Cryan, 2010). Because the demonstration of an anxious phenotype in the corticotrophin-releasing-hormone overexpressing mouse (Heinrichs et al, 1997), knock-out and transgenic mice have played a vital role in both understanding the in vivo function of putative drug targets and now represent the definitive target validation strategy.…”

Section: Ratsmentioning

confidence: 99%

“…Anxiolytic activity in many of the mentioned tests can be confounded by aspects of altered locomotor activity induced by genetic or pharmacological manipulations (Cryan and Holmes, 2005;Holmes and Cryan, 2006;Jacobson and Cryan, 2010). Thus, it is important to consider other tests in batterystyle approaches that are less dependent on motor outputs.…”

Section: Other Anxiety Tests In Laboratory Animalsmentioning

confidence: 99%

“…Because the demonstration of an anxious phenotype in the corticotrophin-releasing-hormone overexpressing mouse (Heinrichs et al, 1997), knock-out and transgenic mice have played a vital role in both understanding the in vivo function of putative drug targets and now represent the definitive target validation strategy. More sophisticated techniques, such as tet-on/off and Cre-lox mediated gene expression systems, as well as siRNA-mediated gene knock down allow temporal and regionally specific control of gene expression in the brain, making transgenic mice an even more useful tool for drug discovery (Gross et al, 2002;Heck et al, 2004;Cryan and Holmes, 2005;Jacobson and Cryan, 2010). Genetic models of anxiety behaviour are listed in Table 3 ( Finn et al, 2003).…”

Section: Ratsmentioning

confidence: 99%

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The age of anxiety: role of animal models of anxiolytic action in drug discovery

Cryan¹,

Sweeney²

2011

British J Pharmacology

236

188

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Anxiety disorders are common, serious and a growing health problem worldwide. However, the causative factors, aetiology and underlying mechanisms of anxiety disorders, as for most psychiatric disorders, remain relatively poorly understood. Animal models are an important aid in giving insight into the aetiology, neurobiology and, ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in humans coupled with the associated multifaceted and descriptive diagnostic criteria, creates challenges in both animal modelling and in clinical research. In this paper, we describe some of the more widely used approaches for assessing the anxiolytic activity of known and potential therapeutic agents. These include ethological, conflict-based, hyponeophagia, vocalization-based, physiological and cognitive-based paradigms. Developments in the characterization of translational models are also summarized, as are the challenges facing researchers in their drug discovery efforts in developing new anxiolytic drugs, not least the ever-shifting clinical conceptualization of anxiety disorders. In conclusion, to date, although animal models of anxiety have relatively good validity, anxiolytic drugs with novel mechanisms have been slow to emerge. It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change.

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Section: Animal Models and Tests Used In Assessing Anxiolytic Actionmentioning

confidence: 99%

Section: Ratsmentioning

confidence: 99%

Section: Other Anxiety Tests In Laboratory Animalsmentioning

confidence: 99%

Section: Ratsmentioning

confidence: 99%

See 2 more Smart Citations

The age of anxiety: role of animal models of anxiolytic action in drug discovery

Cryan¹,

Sweeney²

2011

British J Pharmacology

236

188

View full text Add to dashboard Cite

show abstract

“…Often chronic in nature, these disorders are among the most prevalent mental health problems across the individual life span, producing severe impairments in social and occupational functioning. According to an evolutionary perspective, an anxiety disorder reflects a malfunctioning of the neural circuits responsible for detecting, organizing, or expressing adaptive defense reactions (Jacobson & Cryan, 2010). Humans and nonhuman mammals share approximately the same behavioral defense strategies, reflected by activation of similar underlying neural circuitry.…”

Section: Introductionmentioning

confidence: 99%

The Carioca High and Low Conditioned Freezing Lines: A New Animal Model of Generalized Anxiety Disorder

Gomes¹,

Silva²,

Landeira-Fernández³

2011

Anxiety Disorders

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Preclinical animal anxiety research – flaws and prejudices

Ennaceur

Chazot

2016

Pharmacology Res & Perspec

100

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The current tests of anxiety in mice and rats used in preclinical research include the elevated plus‐maze (EPM) or zero‐maze (EZM), the light/dark box (LDB), and the open‐field (OF). They are currently very popular, and despite their poor achievements, they continue to exert considerable constraints on the development of novel approaches. Hence, a novel anxiety test needs to be compared with these traditional tests, and assessed against various factors that were identified as a source of their inconsistent and contradictory results. These constraints are very costly, and they are in most cases useless as they originate from flawed methodologies. In the present report, we argue that the EPM or EZM, LDB, and OF do not provide unequivocal measures of anxiety; that there is no evidence of motivation conflict involved in these tests. They can be considered at best, tests of natural preference for unlit and/or enclosed spaces. We also argued that pharmacological validation of a behavioral test is an inappropriate approach; it stems from the confusion of animal models of human behavior with animal models of pathophysiology. A behavioral test is developed to detect not to produce symptoms, and a drug is used to validate an identified physiological target. In order to overcome the major methodological flaws in animal anxiety studies, we proposed an open space anxiety test, a 3D maze, which is described here with highlights of its various advantages over to the traditional tests.

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Genetic Approaches to Modeling Anxiety in Animals

Cited by 29 publications

References 260 publications

The age of anxiety: role of animal models of anxiolytic action in drug discovery

The age of anxiety: role of animal models of anxiolytic action in drug discovery

The Carioca High and Low Conditioned Freezing Lines: A New Animal Model of Generalized Anxiety Disorder

Preclinical animal anxiety research – flaws and prejudices

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