The DOI matches its Crossref record.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Animal models of anxiety are widely utilized for neurobiological and pharmacological investigation of anxiety disorders.
“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
Citations
Cited by
Sorted by citations
Regional dissociations within the hippocampus-memory and anxiety
Bannerman, D. M., Rawlins, J. N. P., McHugh, S. B., Deacon, R. M. J., Yee, B. K., Bast, T., Zhang, W.-N., Pothuizen, H. H. J., & Feldon, J. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.03.004 · Cited by 1,462
“Importantly, emotional states exert a strong influence on startle reactivity [71,73]: enhanced startle reactivity is a diagnostic criterion for anxiety disorders in humans and is used as an animal model of anxiety [35,114].”
Bourin, M., & Hascoët, M. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01274-3 · Cited by 1,440
“In the light/dark test, a range of active or passive behaviours, such as freezing, thigmotaxis and risk assessment, are almost invariably ignored in favour of a simple spatiotemporal index (Rodgers, 1997).”
BackgroundThe ascent of mouse: advances in modelling human depression and anxiety
Cryan, J. F., & Holmes, A. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1825 · Cited by 1,198
“Validity of mouse models An issue common to all the various techniques using the mouse to study anxiety and depression is evaluation of the usefulness and validity of mouse model”
Ethological and temporal analyses of anxiety-like behavior: The elevated plus-maze model 20 years on
Carobrez, A. P., & Bertoglio, L. J. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.04.017 · Cited by 993
“However, it is worthy of note that most of the animal tests of anxiety, including the EPM, have been validated pharmacologically by benzodiazepines (Lister, 1990; Green and Hodges, 1991; Rodgers, 1997; Rodgers et al., 1997), and therefore, it would be inappropriate to criticize them for relative insensitivity to agent…”
BackgroundMethodInfluentialThe neurobiology and control of anxious states
Millan, M. J. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00087-x · Cited by 978
Bale, T. L., Contarino, A., Smith, G. W., Chan, R. K. W., Gold, L. H., Sawchenko, P. E., Koob, G. F., Vale, W. W., & Lee, K. (2000) · Nature Genetics · doi:10.1038/74263 · Cited by 850
“Although pharmacological sensitivity and specificity has generally been demonstrated across many animal models of anxiety, task differences are sometimes observe”
BackgroundMeasuring emotional processes in animals: the utility of a cognitive approach
Paul, E. S., Harding, E. J., & Mendl, M. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.01.002 · Cited by 856
“While the reliability and validity of these tests is strengthened by pharmacological and cross-test ‘validation’, there are still problems of interpretation that have been discussed at length by many others [68,117-121].”
The impact of anxiety upon cognition: perspectives from human threat of shock studies
Robinson, O. J., Vytal, K., Cornwell, B. R., & Grillon, C. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00203 · Cited by 613
Scototaxis as anxiety-like behavior in fish
Maximino, C., Brito, T. M., Dias, C. A. G. D. M., Gouvêia, A., & Morato, S. (2010) · Nature Protocols · doi:10.1038/nprot.2009.225 · Cited by 549
“Ex hypothesi , these dimensions are best analyzed using conflict model”
MethodMeasuring anxiety in zebrafish: A critical review
Maximino, C., Brito, T. M., Batista, A. W. D. S., Herculano, A. M., Morato, S., & Gouvêia, A. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.05.031 · Cited by 572
“Among taxonomies of anxiety models in mammals, the most idely used are those which differentiate between learned and nnate behavior [30,38,48,60–63].”
BackgroundMouse Behavioral Assays Relevant to the Symptoms of Autism*
Crawley, J. N. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00096.x · Cited by 541
“Conflict tests including the elevated plus maze, light↔dark exploration, open field emergence, probe burying, marble burying, and Vogel thirsty-lick tests are based on approach–avoidance conflicts and are sensitive to anxiolytic drugs (35, 37, 41, 60, 62, 88, 163, 172).”
BackgroundRole of GABA in anxiety and depression
Kalueff, A. V., & Nutt, D. (2006) · Depression and Anxiety · doi:10.1002/da.20262 · Cited by 563
“…of anxiety, including paradigms based on exploration (open field, holeboard, elevated plus maze, light-dark, social interaction, mirror chamber) and conditioned or unconditioned threat responses [reviewed in Rodgers, 1997; Crawley, 1999, 2000; Flint, 2002, 2003; Carobrez and Bertoglio, 2005].”
BackgroundDesigning mouse behavioral tasks relevant to autistic‐like behaviors
Crawley, J. N. (2004) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.20039 · Cited by 542
Startle reactivity and anxiety disorders: aversive conditioning, context, and neurobiology
Grillon, C. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01665-7 · Cited by 498
“The assumption underlying most animal models of anxiety disorders is that anxiety evolves from defense mechanisms essential for survival, which are highly conserved across species (LeDoux 1995; Rodgers 1997).”
BackgroundDielenberg, R. A., Hunt, G. E., & McGregor, I. S. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00150-6 · Cited by 487
Models and mechanisms of anxiety: evidence from startle studies
Grillon, C. (2008) · Psychopharmacology · doi:10.1007/s00213-007-1019-1 · Cited by 456
“Fear is characterized by flight or fight and anxiety by ‘risk assessment’ behaviors (Blanchard et al. 1993; Rodgers 1997).”
BackgroundMouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic
Blanchard, D. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00009-4 · Cited by 461
“[12]) and, when appropriate ethological measures are added to existing models such as the elevated plus maze [85].”
BackgroundWigger, A., & Neumann, I. D. (1999) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00300-x · Cited by 443
Griebel, G., Belzung, C., Perrault, G., & Sanger, D. J. (2000) · Psychopharmacology · doi:10.1007/s002130050038 · Cited by 420
“Thus, rank order of number of tunnel crossings was SJL=NZB= NMRI>C57BL/6>C3H=DBA/2=CBA=Swiss>BALB/c. motor activity and/or processes unrelated to anxiety and locomotion (File 1992; Belzung and Le Pape 1994; Beuzen and Belzung 1995; Rodgers 1997).”
Background50 years of hurdles and hope in anxiolytic drug discovery
Griebel, G., & Holmes, A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4075 · Cited by 430
Defensive burying in rodents: ethology, neurobiology and psychopharmacology
de Boer, S. F., & Koolhaas, J. M. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01278-0 · Cited by 400
“Consequently, disorders of anxiety can, thus, be viewed as the inappropriate activation or exaggeration of these usually adaptive response patterns (Rodgers, 1997; Nesse, 2000; Rosen and Schulkin, 1998).”
BackgroundThe Open Field Test: reinventing the wheel
Stanford, S. C. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107073199 · Cited by 319
The age of anxiety: role of animal models of anxiolytic action in drug discovery
Cryan, J. F., & Sweeney, F. F. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01362.x · Cited by 327
“…paradigms based on approach–avoidance conflict include the elevated plus maze (Handley and Mithani, 1984; Pellow et al., 1985; Lister, 1987; Rodgers, 1997; Holmes, 2001; Crawley, 2007), elevated zero maze (Lee and Rodgers, 1990; Shepherd et al., 1994), open-field test, light–dark box test…”
BackgroundMethodInfluentialde la Mora, M. P., Gallegos-Cari, A., Arizmendi-García, Y., Marcellino, D., & Fuxe, K. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.10.010 · Cited by 296
“an inhibition of flight may enhance freezing (Rodgers, 1997).”
BackgroundInfluentialAdriaan Bouwknecht, J., Olivier, B., & Paylor, R. E. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2006.02.002 · Cited by 256
Sáenz, J. C. B., Rodríguez‐Villagra, O. A., & Trías, J. F. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.12.001 · Cited by 296
What's wrong with my mouse model?
Kalueff, A. V., Wheaton, M., & Murphy, D. L. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.01.023 · Cited by 285
“predominantly benzodiazepines psychopharmacology for anxiety [298] or serotonin reuptake inhibitors for depression [81] • Use of virtual reality tests in anxiety and depression research (based on recently established rodent sensitivity to virtual environments [156])”
BackgroundWahłsten, D., Bachmanov, A. A., Finn, D. A., & Crabbe, J. C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605342103 · Cited by 280
Effects of developmental exposure to bisphenol A on brain and behavior in mice
Palanza, P., Gioiosa, L., Saal, F. S. V., & Parmigiani, S. (2008) · Environmental Research · doi:10.1016/j.envres.2008.07.023 · Cited by 283
“The elevated-plus-maze paradigm is one of the most widely used animal tests for the study of anxiety (Rodgers, 1997).”
Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze
Emamghoreishi, M., Khasaki, M., & Aazam, M. F. (2004) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2004.06.022 · Cited by 269
Anxiety-Related Behaviors in Mice
Crawley, J. N., & Bailey, K. (2008) · Frontiers in neuroscience · doi:10.1201/noe1420052343.ch5 · Cited by 277
The role of hippocampus in anxiety: intracerebral infusion studies
Engin, E., & Treit, D. (2007) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3282de7929 · Cited by 270
“Rats tend to avoid the open arms of the maze and stay in the enclosed arms (Pellow et al., 1985; Treit et al., 1993; Rodgers, 1997; Carobrez and Bertoglio, 2005).”
BackgroundSpooren, W. P. J. M., Vassout, A., Neijt, H. C., Kuhn, R., Gasparini, F., Roux, S., Porsolt, R. D., & Gentsch, C. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39029-9 · Cited by 266
“…to evaluate the potential of MPEP in a multiplicity of well established animal models of anxiety as recently reviewed by Olivier et al. (2000) and Rodgers (1997), that included a variety of nonconditioned and conditioned anxiety models with a wide range of different behaviors and motivations.”
Tests of unconditioned anxiety — Pitfalls and disappointments
Ennaceur, A. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.05.032 · Cited by 280
“Reductions in the number of rearing has been interpreted as heightened anxiety responses [29,329,331,359], and like grooming, it”
BackgroundInfluentialCorticosterone response to the plus-mazeHigh correlation with risk assessment in rats and mice
Rodgers, R. J., Haller, J., Holmes, A., Halász, J., WALTON, T., & Brain, P. F. (1999) · Physiology & Behavior · doi:10.1016/s0031-9384(99)00140-7 · Cited by 261
Self-citationHippocampal modulation of sensorimotor processes
Bast, T., & Feldon, J. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00112-6 · Cited by 264
“, 1993; Bushnell, 1998) and anxiety (Davis et al., 1997; Rodgers, 1997).”
Methodvan der Staay, F. J. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.01.006 · Cited by 260
Animal models of anxiety disorders in rats and mice: some conceptual issues
Steimer, T. J. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.4/tsteimer · Cited by 242
Behavioral Effects of Acute and Chronic Imipramine in the Elevated T-Maze Model of Anxiety
Teixeira, R. C., Zangrossi, H., & Graeff, F. G. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(99)00261-0 · Cited by 238
Wesołowska, A., Nikiforuk, A., Stachowicz, K., & Tatarczynska, E. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.04.017 · Cited by 230
Basso, A. M., Bratcher, N. A., Harris, R. R., Jarvis, M. F., Decker, M. W., & Rueter, L. E. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.10.018 · Cited by 224
Halloran, J. J., Hussong, S. A., Burbank, R. R., Podlutskaya, N., Fischer, K. E., Sloane, L. B., Austad, S. N., Strong, R., Richardson, A. G., Hart, M. J., et al. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.06.054 · Cited by 223
“The elevated plus maze was used to assess emotionality and reactivity (Rodgers, 1997).”
A Review of Behavioral Tests to Evaluate Different Types of Anxiety and Anti-anxiety Effects
Himanshu, Dharmila, Sarkar, D., & Nutan, N. (2020) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2020.18.3.341 · Cited by 217
“As per the previous studies, Rodger in 1997 found that the difference in locomotor activities of individual confound the measure of emotionality which follows that the difference in emotionality of individual will confound the locomotor activity [47].”
MethodEffect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety
Lovick, T. A., & Zangrossi, H. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.711065 · Cited by 234
Grillon, C., Baas, J. M. P., Cornwell, B., & Johnson, L. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.072 · Cited by 209
Analysis of quantitative trait loci that influence animal behavior
Jonathan Flint, C. (2002) · Journal of Neurobiology · doi:10.1002/neu.10161 · Cited by 210
“Rats tend to avoid the open elevated alleys and prefer the closed alleys, a preference that is considered to be driven at least in part by fearfulness (Hogg, 1996; Montgomery, 1958; Rodgers, 1997 ).”
BackgroundSmith, R. J., & Aston-Jones, G. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0191-3 · Cited by 206
“…paradigms, including the elevated plus-maze, open field, acoustic startle reflex, and the social interaction test, and are indexed by levels of exploratory or social behavior, freezing, startle, or vocalizations (Davis 1993; File 1990; Pellow et al. 1985; Prut and Belzung 2003; Rodgers 1997).”
BackgroundBehavioral and physiological mouse assays for anxiety: a survey in nine mouse strains
Bouwknecht, J. A., & Paylor, R. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00200-0 · Cited by 209
The effects of chronic treadmill and wheel running on behavior in rats
Burghardt, P. R., Fulk, L. J., Hand, G. A., & Wilson, M. A. (2004) · Brain Research · doi:10.1016/j.brainres.2004.05.086 · Cited by 204
Differences in Measures of Exploration and Fear in MHC-Congenic C57BL/6J and B6-H-2K Mice
Brown, R. E., Corey, S. C., & Moore, A. K. (1999) · Behavior Genetics · doi:10.1023/a:1021694307672 · Cited by 205
Rearing environmental enrichment in two inbred strains of mice: 1. Effects on emotional reactivity
Chapillon, P., Manneché, C., Belzung, C., & Caston, J. (1999) · Behavior Genetics · doi:10.1023/a:1021437905913 · Cited by 202
Targeted gene mutation approaches to the study of anxiety-like behavior in mice
Holmes, A. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00012-4 · Cited by 198
Shah, A. A., & Treit, D. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02299-6 · Cited by 196
Parametric analyses of anxiety in zebrafish scototaxis
Maximino, C., Brito, T. M., Colmanetti, R., Pontes, A. A. A., de Castro, H. M., de Lacerda, R. I. T., Morato, S., & Gouvêia, A. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.01.031 · Cited by 197
QTL Analysis of Multiple Behavioral Measures of Anxiety in Mice
Henderson, N. D., Turri, M. G., DeFries, J. C., & Jonathan Flint, C. (2004) · Behavior Genetics · doi:10.1023/b:bege.0000017872.25069.44 · Cited by 192
Effects of transgenic overproduction of CRH on anxiety‐like behaviour
van Gaalen, M. M., Stenzel‐Poore, M. P., Holsboer, F., & Steckler, T. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02040.x · Cited by 189
“…that the measures of anxiety-like behaviour assessed in different tests may re¯ect different aspects of anxiety-like behaviour in rodents (Griebel et al., 1993, 1997, 1999, 2000; Belzung & Le Pape, 1994; Beuzen & Belzung, 1995; Rodgers, 1997; Kopp et al., 1999; van Gaalen & Steckler, 2000).”
BackgroundOntogeny of fear-, anxiety- and depression-related behavior across adolescence in C57BL/6J mice
HEFNER, K., & HOLMES, A. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.10.001 · Cited by 183
“Anxietylike behaviors were measured using two pharmacologically well-validated exploration-based tests, elevated plus-maze and novel open field [11,42].”
MethodContet, C. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00231-5 · Cited by 176
“This increased activity was marked and significant for closed arm entries, which most closely reflect a general activity factor [35].”
BackgroundMazella, J., Pétrault, O., Lucas, G., Deval, E., Béraud-Dufour, S., Gandin, C., Yacoubi, M. E., Widmann, C., Guyon, A., Chevet, É., et al. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000355 · Cited by 193
“Avoidance behaviors are reduced by treatments with clinically efficacious anxiolytics, mainly by the benzodiazepine agonist class, including diazepam [36].”
Is There a Future for Neuropeptide Receptor Ligands in the Treatment of Anxiety Disorders?
Griebel, G. (1999) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(98)00041-2 · Cited by 171
“However, the use of different experimental procedures may account for this variability, since there is now growing evidence that different animal models of anxiolytic activity actually may be measuring different facets of anxiety (Rodgers, 1997; Ramos and Mormede, 1998).”
BackgroundBoucher, A. A., Arnold, J. C., Duffy, L., Schofield, P. R., Micheau, J., & Karl, T. (2007) · Psychopharmacology · doi:10.1007/s00213-007-0721-3 · Cited by 168
“This task-dependent anxiolytic phenotype suggests an impact of Nrg1 on certain explorative/locomotive aspects of anxiety (Rodgers 1997; Rodgers and Johnson 1995).”
BackgroundGenetic animal models of anxiety
Finn, D. A., Rutledge-Gorman, M. T., & Crabbe, J. C. (2003) · Neurogenetics · doi:10.1007/s10048-003-0143-2 · Cited by 166
“As is the case with any complex human disorder, the validity of the animal models employed is of major importance, an issue that has been addressed in several excellent reviews [1, 2, 3].”
Actions of essential oils on the central nervous system: An updated review.
Dobetsberger, C., & Buchbauer, G. (2011) · Flavour and Fragrance Journal · doi:10.1002/ffj.2045 · Cited by 163
TMT-induced autonomic and behavioral changes and the neural basis of its processing
Fendt, M., Endres, T., Lowry, C. A., Apfelbach, R., & McGregor, I. S. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.04.018 · Cited by 158
“In particular, this includes face validity, construct validity, and predictive validity (Hogg, 1996; Rodgers, 1997).”
BackgroundAnti-anxiety effects of Apocynum venetum L. in the elevated plus maze test
Grundmann, O., Nakajima, J., Seo, S., et al. (2006) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2006.09.035 · Cited by 159
Haller, J., Barna, I., Barsvari, B., Gyimesi Pelczer, K., Yasar, S., Panlilio, L. V., & Goldberg, S. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1494-7 · Cited by 159
“Discrepancies such as these are not unusual in anxiety research (see Haller et al. 2004a, a nd Rodgers 1997 for reviews).”
Home cage activity and behavioral performance in inbred and hybrid mice
Tang, X., Orchard, S. M., & Sanford, L. D. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00228-0 · Cited by 154
Dielenberg, R. A., Carrive, P., & McGregor, I. S. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02227-2 · Cited by 152
The Vogel conflict test: procedural aspects, γ-aminobutyric acid, glutamate and monoamines
Millan, M. J., & Brocco, M. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01275-5 · Cited by 149
SEE: a tool for the visualization and analysis of rodent exploratory behavior
Drai, D., & Golani, I. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00022-7 · Cited by 149
Behavioral profile of wild mice in the elevated plus-maze test for anxiety
Holmes, A., Parmigiani, S., Ferrari, P. F., Palanza, P., & Rodgers, R. J. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(00)00373-5 · Cited by 148
“In the conventional form of the test, anxiety is routinely assessed by measures of open arm avoidance while locomotor activity is most reliably measured by the frequency of closed arm entries [2].”
BackgroundMethodSelf-citationNew replicable anxiety-related measures of wall vs. center behavior of mice in the open field
Lipkind, D., Sakov, A., Kafkafi, N., Elmer, G. I., Benjamini, Y., & Golani, I. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00148.2004 · Cited by 143
“More comprehensive analyses of tests of unconditioned behavior are needed (30, 31, 38) that would provide detailed and articulated information about different aspects of the animal’s behavior, thus allowing for the reliable interpretation of genetic and pharmacological results.”
BackgroundCampbell, B. M., & Merchant, K. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03384-5 · Cited by 144
Ducottet, C., & Belzung, C. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.05.018 · Cited by 151
Effects of medial prefrontal cortex cytotoxic lesions in mice
Deacon, R. M. J., Penny, C., & Rawlins, J. N. P. (2003) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00225-5 · Cited by 143
Madani, R., Kozlov, S. V., Akhmedov, A. T., Cinelli, P., Kinter, J., Lipp, H., Sonderegger, P., & Wolfer, D. P. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(03)00077-0 · Cited by 140
Henniger, M. S. H., Ohl, F., Hölter, S. M., Weißenbacher, P., Toschi, N., Lörscher, P., Wigger, A., Spanagel, R., & Landgraf, R. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00151-0 · Cited by 135
Animal models of CNS disorders
McGonigle, P. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.06.016 · Cited by 142
Dimensions of emotionality in a rat model of innate anxiety.
Ohl, F., Toschi, N., Wigger, A., Henniger, M. S. H., & Landgraf, R. (2001) · Behavioral Neuroscience · doi:10.1037/0735-7044.115.2.429 · Cited by 134
An Assessment of Anxiolytic Drug Screening Tests: Hormetic Dose Responses Predominate
Calabrese, E. J. (2008) · Critical Reviews in Toxicology · doi:10.1080/10408440802014238 · Cited by 132
“(Source: Cao and Rodgers, 1997, Table 1, p. 599). ing through about a dozen different receptors reveals strikingly similar quantitative features of the dose response as seen by the magnitude and width of the stimulatory responses.”
BackgroundPreclinical animal anxiety research – flaws and prejudices
Ennaceur, A., & Chazot, P. L. (2016) · Pharmacology Research & Perspectives · doi:10.1002/prp2.223 · Cited by 131
“These TUA have been subjects of numerous reviews, which highlighted their shortcomings concerning their sensitivity and some aspects of their validity (Belzung and Griebel 2001; Belzung 2001; Crabbe et al. 1999; Cryan and Sweeney 2011; Dawson and Tricklebank 1995; Griebel and Holmes 2013; Hogg 1996; Milner and Crabbe…”
BackgroundThree murine anxiety models: results from multiple inbred strain comparisons
Milner, L. C., & Crabbe, J. C. (2007) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2007.00385.x · Cited by 128
“These tests require no conditioning, do not cause physical discomfort and are considered to have ecological face validity (Rodgers 1997).”
BackgroundAugustsson, H., & Meyerson, B. J. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.03.014 · Cited by 125
Anxiogenic-like effect of chronic corticosterone in the light-dark emergence task in mice.
Ardayfio, P. A., & Kim, K. (2006) · Behavioral Neuroscience · doi:10.1037/0735-7044.120.2.249 · Cited by 123
“Journal of Comparative Neurology, 285, 413–435. Thompson, B. L., Erickson, K., Schulkin, J., & Rosen, J. B. (2004). Corticosterone facilitates retention of contextually conditioned fear and increases CRH mRNA expression in the amygdala.”
BackgroundFendt, M., Siegl, S., & Steiniger‐Brach, B. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1028-05.2005 · Cited by 118
“These autonomic and behavioral changes are common to fear (Olivier et al., 1994; Rodgers, 1997; Fendt, 2005), indicating that TMT is, similar to cat odor, a natural stimulus, which innately induces fear in rodents (Fendt et al.”
BackgroundHolmes, A., & Rodgers, R. J. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00030-5 · Cited by 121
“The elevated plus-maze is currently one of the most widely used animal models for the study of drug effects on anxiety [1,2].”
Self-citationVocalizations during withdrawal from opiates and cocaine: possible expressions of affective distress
Covington, H. E., & Miczek, K. A. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01558-9 · Cited by 121
Gulinello, M. E., & Smith, S. S. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.045120 · Cited by 116
“Use of both tests, as in the present study, provides a more complete analysis of the behavioral state to both proximal and distal threats produced by 48-h steroid exposure (Rodgers, 1997).”
Brain Neuropeptide Υ (NPY) in Stress and Alcohol Dependence
Heilig, M. A., & Thorsell, A. (2002) · Reviews in the Neurosciences · doi:10.1515/revneuro.2002.13.1.85 · Cited by 114
Animals, anxiety, and anxiety disorders: How to measure anxiety in rodents and why
Harro, J. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.10.016 · Cited by 122
The modified hole board as a differential screen for behavior in rodents
Ohl, F., Holsboer, F., & Landgraf, R. (2001) · Behavior Research Methods, Instruments, & Computers · doi:10.3758/bf03195393 · Cited by 113
“…the behavior of rodents is context dependent, and, when characterizing novel animal models, distinct behavioral tests frequently produce conflicting results in that one behavioral dimension displayed by the same strain differs between distinct tests (Rodgers, 1997; Trullas & Skolnick,1993).”
BackgroundPandey, D. K., Yadav, S. K., Mahesh, R., & Rajkumar, R. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.07.027 · Cited by 112
Brocco, M., Dekeyne, A., Veiga, S., Girardon, S., & Millan, M. J. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00701-8 · Cited by 110
Cocaine potentiates defensive behaviors related to fear and anxiety
Blanchard, D. C., & Blanchard, R. J. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00031-7 · Cited by 110
Non-human primate models for investigating fear and anxiety
Barros, M., & Tomaz, C. A. B. (2002) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00064-1 · Cited by 109
Alves, S. H. D. S., Pinheiro, G. D. A., Motta, V., Landeira-Fernández, J., & Cruz, A. P. D. M. (2004) · Behavioural Pharmacology · doi:10.1097/00008877-200402000-00005 · Cited by 106
“In this respect, similar inconsistencies with different 5-HT-acting drugs have been observed in several animal models (for reviews see Griebel, 1995; Rodgers, 1997; Menard and Treit, 1999).”
BackgroundRoy, V., & Chapillon, P. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.03.010 · Cited by 104
“In particular, risk assessment and avoidance behaviours seem to faithfully represent the approach/avoidance conflict in a novel situation and detailed ethological analyses have been recently applied to standard tests of emotional reactivity [10,49–53,66].”
Graef, S., Schönknecht, P., Sabri, O., & Hegerl, U. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2153-8 · Cited by 107
“Anxiety models used in rodents comprise several different tests, e.g. the shock–probe burying test, social interaction test, open field tasks, the elevated plus maze, the mirrored chamber as well as the fear-potentiated startle response (Picciotto et al. 2002; Rodgers 1997).”
MethodModulation of mice anxiety in response to cat odor as a consequence of predators diet
Berton, F., Vogel, E., & Belzung, C. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00126-7 · Cited by 105
Fakhfouri, G., Rahimian, R., Dyhrfjeld‐Johnsen, J., Zirak, M. R., & Beaulieu, J. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.015487 · Cited by 105
“The animal tasks commonly used to test the anxiolytic properties of compounds comprise rodent conflict models of anxiety such as the dark-light emergence test, exploration tests including the elevated plus maze and open field tests, and social tasks such as social competition and social interaction tests (Rodgers, 199…”
Method
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
