Animal Models of Anxiety and Anxiolytic Drug Action

Treit, Dallas; Engin, Elif; McEown, Kristopher

doi:10.1007/7854_2009_17

Cited by 48 publications

(49 citation statements)

References 311 publications

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“…The apparent insensitivity of many of the tests to commonly used clinical anxiolytics, such as the SSRIs, is a major concern (Borsini et al, 2002), and questions still linger as to the fact that the maintenance of anxiety disorders is ultimately based on cognitive processes only present in humans, as evidenced by the efficacy of cognitive treatments in humans (Steckler et al, 2008). In order to advance the efforts in drug discovery, we must both re-assess our concepts of validity (Treit et al, 2010). It is also important to remember that our animal models are only as valid as the knowledge of the neurobiology and pathophysiology of clinical anxiety disorders that underpin their design.…”

Section: Discussionmentioning

confidence: 99%

“…This is based on the variable effects produced by SSRI across the spectrum of anxiety tests with the notable exceptions of the USV suppression, MDTB and defensive marble burying paradigms (Rodgers, 1997;Borsini et al, 2002;Blanchard, 2003;Markou et al, 2009). It should, however, be remembered that many of the currently used behavioural tests were developed based on prevailing clinical practice that clearly distinguished between the anxiety disorders and depression in terms of both symptom presentation and treatment, with the gold standard of predictive validity as benzodiazepine sensitivity (Treit et al, 2010). Nevertheless, a variety of putative anxiolytic compounds have shown efficacy in a variety of SSRI-sensitive behavioural tests.…”

Section: Pharmacological Validationmentioning

confidence: 99%

“…In the context of anxiety, it has been argued by Treit et al (2010) that the validity of behavioural tests of anxiety should be based on three principles arising from the evolutionarily conserved roles the fear response plays in normal survival behaviour. Firstly, a correspondence between the behavioural fear expressions in the animal model biochemical or physiological correlates of these behaviours, and the expression of isomorphic behavioural responses in humans.…”

Section: Basic Concepts In Animal Modelling Of Anxiety Disordersmentioning

confidence: 99%

“…Secondly, if no isomorphism is present, biological function should be conserved between the anxiety-like behaviour in the animal model and the human fear response. And thirdly, conservation of the neural mechanisms, engaged during the fear response, that underlie anxiety-related behaviour in both animals and humans (Treit et al, 2010).…”

Section: Basic Concepts In Animal Modelling Of Anxiety Disordersmentioning

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

230

185

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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: Discussionmentioning

confidence: 99%

Section: Pharmacological Validationmentioning

confidence: 99%

Section: Basic Concepts In Animal Modelling Of Anxiety Disordersmentioning

confidence: 99%

Section: Basic Concepts In Animal Modelling Of Anxiety Disordersmentioning

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

230

185

View full text Add to dashboard Cite

show abstract

“…Second, SST in some amygdalar neurons is both co-localized and co-released with GABA . GABA, through the GABA A receptor and an allosteric binding site for benzodiazepines, modulates both experimental anxiety in animals and clinical anxiety in humans (Treit et al 2010). Third, SST receptor gene expression in the amygdala is increased by predatory stress (Nanda et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Anxiolytic-like effects of somatostatin isoforms SST 14 and SST 28 in two animal models (Rattus norvegicus) after intra-amygdalar and intra-septal microinfusions

2011

Self Cite

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SST receptors in the septum and amygdala are responsive to both SST 14 and SST 28, but not those in the striatum. Although no obvious differences in the anxiolytic-like effects of the isoforms were detected, quantitative or even qualitative differences in their specific anxiolytic effects may occur in different sub-regions of the septum and amygdala, as has been found for benzodiazepine anxiolytics.

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Preclinical animal anxiety research – flaws and prejudices

Ennaceur

Chazot

2016

Pharmacology Res & Perspec

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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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Animal Models of Anxiety and Anxiolytic Drug Action

Cited by 48 publications

References 311 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

Anxiolytic-like effects of somatostatin isoforms SST 14 and SST 28 in two animal models (Rattus norvegicus) after intra-amygdalar and intra-septal microinfusions

Preclinical animal anxiety research – flaws and prejudices

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