Do animal models of anxiety predict anxiolytic-like effects of antidepressants?
Abstract
Chronically administered antidepressant drugs, particularly selective serotonin (5-HT) reuptake inhibitors (SSRIs), are clinically effective in the treatment of all anxiety disorders, while the clinical effectiveness of "traditional" anxiolytics, such as benzodiazepines (BDZs), is limited to generalised anxiety disorder or acute panic attacks. This implies that animal models of anxiety should be sensitive to SSRIs and other antidepressants in order to have predictive validity. We reviewed the literature on the effects of antidepressants in the so-called animal models of anxiety and found that only the isolation-induced calls in guinea-pig pups may reveal anxiolytic-like action of all antidepressant classes after acute administration. Some other models, such as marble-burying or conditioned-freezing behaviours, and isolation- or shock-induced ultrasonic vocalisation models, may detect anxiolytic-like activity of acutely administered antidepressants, although the sensitivity of these models is usually limited to SSRIs and other drugs affecting 5-HT uptake. The predictive validity of models of "anxiety", such as the plus-maze and light-dark transition tests or stress-induced hyperthermia, appears to be limited to BDZ-related drugs. Far less work has been done on chronic administration of antidepressants in animal anxiety models. Unless and until such studies have been undertaken, the true predictive value of the anxiety models will remain unknown.
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The marble-burying test is widely used in the field of anxiety research.
“leading to the test being widely used in the field of anxiety research [88].”
From Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders (2016) · cites this paper as [88]
Both antidepressant drugs and antianxiety drugs have been shown to reduce marble burying behavior.
“Both antidepressant drugs and antianxiety drugs have been shown to reduce marble burying behavior”
From Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders (2016) · cites this paper as [88]
Anxiety-like behaviors in approach-avoidance tasks are reduced by anxiolytic drugs, particularly benzodiazepines.
“Furthermore, anxiety-like behaviors in these tasks are reduced by anxiolytic drugs, particularly benzodiazepines42.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [42]
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Nishikawa, H., Inoue, T., Izumi, T., & Koyama, T. (2007) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2007.02.010 · Cited by 58 · see citing works
Altered anxiety-related behavior in nociceptin/orphanin FQ receptor gene knockout mice
Gavioli, E. C., Rizzi, A., Marzola, G., Zucchini, S., Regoli, D. C., & Calò, G. (2007) · Peptides · doi:10.1016/j.peptides.2007.04.012 · Cited by 58 · see citing works
Molecular Targets of Anxiety: From Membrane to Nucleus
Wu, L., Kim, S. S., & Zhuo, M. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9679-8 · Cited by 57 · see citing works
The Elevated Plus-Maze Test: Differential Psychopharmacology of Anxiety-Related Behavior
Pawlak, C. R., Karrenbauer, B. D., Schneider, P., & Ho, Y. (2012) · Emotion Review · doi:10.1177/1754073911421374 · Cited by 57 · see citing works
Models of anxiety: Responses of mice to novelty and open spaces in a 3D maze
Ennaceur, A., Michalíková, S., VANRENSBURG, R., & Chazot, P. L. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.07.001 · Cited by 54 · see citing works
Anosmia does not impair the anxiolytic-like effect of lavender essential oil inhalation in mice
Chioca, L. R., Antunes, V. D., Ferro, M. M., Losso, E. M., & Andreatini, R. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.03.012 · Cited by 55 · see citing works
Serotonin transporter density and anxiolytic-like effects of antidepressants in mice
Mirza, N. R., Nielsen, E. Ø., & Troelsen, K. B. (2007) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2007.01.020 · Cited by 55 · see citing works
- Authors
- Borsini, F., Podhorna, J., & Marazziti, D.
- Affiliations
- Boehringer Ingelheim (Germany) (DE)
- University of Pisa (IT)
- ORCID
- Marazziti, Donatella
- Venue
- Psychopharmacology
- Published
- 2002-09-01
- Volume
- 163
- Issue
- 2
- Pages
- 121-141
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2069192879
- Cited by
- 347
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 12 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 11 · 2018: 14 · 2017: 12 · 2016: 14 · 2015: 17 · 2014: 21 · 2013: 9 · 2012: 12
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- animal models of anxiety, antidepressants, anxiolytic-like effects, selective serotonin reuptake inhibitors, benzodiazepines, predictive validity, marble burying test, conditioned freezing, ultrasonic vocalizations, plus-maze test, light-dark transition test, stress-induced hyperthermia, anxiety disorders
- MeSH terms
- Animals, Antidepressive Agents, Tricyclic, Anxiety, Disease Models, Animal, Forecasting, Humans, Anti-Anxiety Agents
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