Behavioural and pharmacological characterisation of the elevated “zero-maze” as an animal model of anxiety
Abstract
The elevated "zero-maze" is a modification of the elevated plus-maze model of anxiety in rats which incorporates both traditional and novel ethological measures in the analysis of drug effects. The novel design comprises an elevated annular platform with two opposite enclosed quadrants and two open, removing any ambiguity in interpretation of time spent on the central square of the traditional design and allowing uninterrupted exploration. Using this model, the reference benzodiazepine anxiolytics, diazepam (0.125-0.5 mg/kg) and chlordiazepoxide (0.5-2.0 mg/kg) significantly increased the percentage of time spent in the open quadrants (% TO) and the frequency of head dips over the edge of the platform (HDIPS), and reduced the frequency of stretched attend postures (SAP) from the closed to open quadrants. In contrast, the anxiogenic drug m-chlorophenyl-piperazine (mCPP; 0.25-1.0 mg/kg) induced the opposite effects, decreasing %TO and HDIPS, and increasing SAP. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.001-0.1 mg/kg) had no effects on either %TO or HDIPS, but did decrease SAP at 0.01 mg/kg although not at higher or lower doses. Similarly, the 5-HT3 receptor antagonist, ondansetron (0.0001-1.0 mg/kg) decreased SAP and increased %TO at 0.01 mg/kg, but not at other doses. The present data suggest that a combination of the novel "zero-maze" design and a detailed ethological analysis provides a sensitive model for the detection of anxiolytic/anxiogenic drug action.
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In the elevated zero maze, anxious mice prefer the walled quadrants to the open ones.
“The ambiguous center of the EPM is eliminated in the elevated zero maze; however, the task resembles the EPM otherwise in that anxious mice prefer the walled quadrants to the open ones36.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [36]
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- Authors
- Shepherd, J. K., Grewal, S. S., Fletcher, A., Bill, D. J., & Dourish, C. T.
- Venue
- Psychopharmacology
- Published
- 1994-09
- Volume
- 116
- Issue
- 1
- Pages
- 56-64
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2001308670
- Cited by
- 739
- References
- 55
- Citations by year
- 2026: 27 · 2025: 26 · 2024: 29 · 2023: 29 · 2022: 20 · 2021: 34 · 2020: 36 · 2019: 22 · 2018: 29 · 2017: 17 · 2016: 25 · 2015: 39 · 2014: 33 · 2013: 36 · 2012: 32
- FWCI
- 3.62
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- anxiety models, elevated plus maze, benzodiazepines, diazepam, chlordiazepoxide, 5-HT1A receptor agonist, 8-OH-DPAT, 5-HT3 receptor antagonists, ondansetron
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Chlordiazepoxide, Diazepam, Disease Models, Animal, Dose-Response Relationship, Drug, Male, Piperazines, Posture, Anti-Anxiety Agents, Rats, Sprague-Dawley, Ondansetron, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, Rats
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