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Animal models of ‘anxiety’: Where next?
Abstract
Numerous procedures have been developed to facilitate preclinical research on the behavioural pharmacology of anxiety and, as a result of this application, are often referred to as animal models of 'anxiety'. This is an unfortunate misnomer, not only because of the apparent inability of many tests to detect novel anxiolytics consistently, but also because the term implies that anxiety is a unitary emotion. Such difficulties have arisen largely as a consequence of test development strategies which, by emphasizing pharmacological (i.e. benzodiazepine) validation, have yielded models predictive of a specific type of anxiolytic activity. The present review argues that the refinement of existing tests as well as the development of new procedures requires urgent attention to the much neglected issue of behavioural validation. From an evolutionary perspective, normal human anxiety may be conceptualized as a repertoire of defence reactions tailored to meet different forms of threats, and disorders of anxiety as the inappropriate activation or exaggeration of these usually adaptive response patterns. In this context, consideration of the defensive reactions typically observed in our animal models reveals substantially greater commonality in the behavioural effects of benzodiazepine and 5-HT1A anxiolytics than would otherwise be apparent. Therefore, with the exception of the conventional plus-maze paradigm (discussed at some length), better correspondence is seen in tests involving unconditioned response to potential threat (e.g. social interaction, distress vocalizations and light/dark exploration) than in tests of conditioned fear reactions. Even within the latter grouping, however, greater commonality is seen in procedures based on reactions to proximal threat (e.g. freezing, startle, ultrasonic vocalizations, burying) than those involving reactions to distal threat (e.g. avoidance/flight). Significantly, very similar findings have been reported in tests specifically designed to study defensive reactions (e.g. rat and mouse defence test batteries) or which incorporate a more detailed knowledge of defence into established procedures (e.g. ethological plus-maze and defensive burying paradigms). Furthermore, recent evidence also suggests that drugs with proved clinical efficacy in panic attacks/panic disorder have reliably stronger effects on flight responses than other components of the defensive repertoire. It is concluded that a focus on defensive behaviour patterns improves test validity (predictive/face/construct), offers a more rational basis for test selection in drug development programmes, and provides a firmer theoretical framework for future methodological and therapeutic advance.
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“Animal models of anxiety have been widely utilized for the neurobiological and pharmacological investigation of the anxiety disorders (Rodgers, 1997).”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Rodgers, 1997
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Items 401–435 of 435
Skolnick, P. (2000) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-8470-9_10
Jacobson, L. H. (2007) · edoc (University of Basel) · doi:10.5451/unibas-004290851
“Examples of these tasks include the aversion to the open central area of novel open fields (see (Prut and Belzung 2003)), avoidance of brightly lit spaces in the light-dark box test (Crawley 2000), and avoidance of elevated and/or open spaces in the elevated plus maze (Crawley 2000; Holmes 2001; Rodgers 1997), elevate…”
BackgroundMethodInfluentialGanev, J. (2007) · UC Research Repository (University of Canterbury) · doi:10.26021/6092
Understanding the causes of anxiety
Simpson, H. B., Neria, Y., Lewis‐Fernández, R., & Schneier, F. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511777578.015
GABA A alpha-5 subunit manipulation of maternal separation-induced anxiety in mice
Sloley, S. S., Hwa, L. S., DeBold, J. F., Miczek, K. A., & Thesis, H. (2011)
The Lateral Septum and the Regulation of Anxiety
Chee, S. A. (2013) · QSpace (Queen's University Library)
Lateral Septal Regulation of Anxiety
Trent, N. L. (2012) · QSpace (Queen's University Library)
Role of arginine vasopressin in modulating plasticity in defensive behavior
Shantala, A. H. D. (2014) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/61632
Gerlai, R. T., Blanchard, R. J., & Blanchard, C. (2006) · Contemporary clinical neuroscience · doi:10.1007/978-1-59745-058-4_11
de Psicología, D., & Psicobiologia, P. D. P. E. (2011)
Kamino, D. (2012) · uO Research (University of Ottawa) · doi:10.20381/ruor-5930
“Thus, although exploratory-based approach-avoidance tests have a high degree of ecological validity (Rodgers, 1997), their limitations highlight the need for alternate methods to aid in the investigation of anxiety- and fear-related behaviour in animals.”
Backgroundda Silva, L. C. C. P., Chumbinho, L. C., Pizzini, C. C., Batista, W. S., de Oliveira, F. S., & de Oliveira, G. M. (2012) · Americanae (AECID Library)
Emotional regulation and the limbic system associated membrane protein.
Catania, E. H. (2008) · Europe PMC (PubMed Central)
Dykstra, C. M. (2013) · TSpace (University of Toronto)
Al-Abkal, F., Zaitone, S. A., & Moustafa, Y. M. (2018) · Records of Pharmaceutical and Biomedical Sciences/Records of Pharmaceutical & Biomedical Sciences · doi:10.21608/rpbs.2018.5918
Adolescent anabolic steroid exposure alters anxiety through aggression circuits
Morrison, T. R. (2016) · Digital Repository Service (Northeastern University) · doi:10.17760/d20213405
Alghamdi, B. S. A. (2019) · Medical Archives · doi:10.5455/medarh.2019.73.222-227
“The settings or procedures used to record these responses are usually called “tests” and represent tools to assess and quantify changes associated with anxiety (6).”
Maximino, C. (2012) · SpringerBriefs in neuroscience · doi:10.1007/978-1-4614-4048-2_1
Developmental neurotoxicity of drugs of abuse
Multani, P. K., Saini, N., Kalra, R. S., Kandimalla, R. J. L., & Saini, V. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-89773-0.00019-9
Nestler, E. J. (2010) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.3113960.2797058
Crawley, J. N. (2006) · Wiley eBooks · doi:10.1002/9780470119051.refs
(2010) · Elsevier eBooks · doi:10.1016/b978-0-12-375674-9.10021-7
Becker, A., Helmuth, M., & Chindo, B. A. (2023) · OBM Neurobiology · doi:10.21926/obm.neurobiol.2304200
Curdt, N. (2024) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-10405
Archana Gaur, T., Sengupta, T., Ghosh, S., Maithilikarpagaselvi, N., & Nayak, P. (2025) · Annals of Neurosciences · doi:10.1177/09727531251319084
LeVasseur, G. W., Cilley, T., Szewczuk, M., Perrine, S. A., & Norrholm, S. D. (2025) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2025.1727468
“A parametric discussion of FPS versus freezing as an index of threat, fear, or anxiety-like behaviors is beyond the scope of the current study and has been discussed elsewhere (Rodgers, 1997; Rosen and Schulkin, 1998; Fendt and Fanselow, 1999; Pare et al., 2004).”
Autonomic function in mice with altered anxiety/depression related behavior
Gaburro, S. (2009) · Padua Research Archive (University of Padova)
de Souza, J. A., Pimentel, G. A., & Florindo, L. H. (2026) · Behavioural Brain Research · doi:10.1016/j.bbr.2026.116036
Rodriguez, J. L. R. (2011) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.59.2011.tde-27042011-151313
Anxiety and Fear, Neural Basis of
Radulović, J., & Spiess, J. (2001) · Elsevier eBooks · doi:10.1016/b0-08-043076-7/03591-9 · Cited by 1
Hopko (2000) · doi:10.1002/1520-6394(2000)12:4
Metadata
- Authors
- Rodgers, R. J.
- Affiliations
- University of Leeds (GB)
- Corresponding author
- Rodgers, R J
- Venue
- Behavioural Pharmacology
- Published
- 1997-11
- Volume
- 8
- Issue
- 6
- Pages
- 477-496
- ISSN
- 0955-8810 (ISSN-L)
- OpenAlex
- W2076532454
- Cited by
- 437
- References
- 0
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 1 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 10 · 2016: 10 · 2015: 15 · 2014: 22 · 2013: 22 · 2012: 21
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- animal models of anxiety, defensive reactions, benzodiazepines, 5-HT1A receptor agonist, defensive burying, panic disorder, threat response, test validity
- MeSH terms
- Animals, Anxiety, Disease Models, Animal, Humans
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