Validation of a simple, ethologically relevant paradigm for assessing anxiety in mice
Abstract
Although numerous behavioral tests are available to assess anxiety, we introduce a simplified version of a previously established test that is exquisitely sensitive and reliable. The latency to consume a palatable snack (graham wafer crumbs) was assessed among mice in their home cage and in an unfamiliar environment, as well as in the presence or absence of predator scent. The effects of various anxiolytics and nonanxiolytics were evaluated in these paradigms. When offered the palatable snack in a familiar environment, mice readily approached and began consumption; however, in a novel environment (cage with fresh bedding), or in the presence of predator scent (rat feces), response latencies increased 10-fold. Anxiolytics, including diazepam, chlordiazepoxide, propranolol, or chronic treatment with either buspirone or the antidepressant desmethylimipramine attenuated the effects in the novel environment without affecting home-cage responding. In contrast, nonanxiolytic agents (haloperidol, amphetamine, acute buspirone or desmethylimipramine) failed to exclusively affect novel environment-induced prolongation of response latencies. The simplicity of design, the absence of food deprivation or neurogenic stressors, the possibility of using it in a repeated measures design, the reliability and magnitude of response, and the specificity and sensitivity to anxiolytic drugs makes this an ideal preparation with which to assess anxiety and anxiety-altering manipulations.
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The NIH test responds to acute benzodiazepine treatment, including CDP.
“In the NIH test, the reduction in feeding in response to a novel environment is a well established measure for anxiety-related behaviors (Dulawa and Hen, 2005) and is sensitive to acute benzodiazepine administration, such as CDP (Merali et al., 2003).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Merali et al., 2003
The NSF test includes food deprivation, which is itself a stressor and may confound determination of anxiogenic responses to a novel environment.
“One significant difference between the paradigms is that the NSF test includes food deprivation, which is itself a stressor, and may present a confounding factor in the determination of anxiogenic responses arising from a novel environment (Merali et al., 2003).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Merali et al., 2003
In a novel environment, hungry mice exhibit an increased latency to feed that is sensitive to benzodiazepines and SSRIs.
“Hyponeophagia (novelty-suppressed feeding) has also been used to assess anxiety-like behavior in rodents; in a novel environment, hungry mice exhibit an increased latency to feed that is sensitive to benzodiazepines and SSRIs47,48.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [48]
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- Authors
- Merali, Z., Levac, C., & Anisman, H.
- Affiliations
- University of Ottawa (CA)
- Corresponding author
- Anisman, Hymie
- ORCID
- Merali, Zul
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 54
- Issue
- 5
- Pages
- 552-565
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2082606474
- Cited by
- 157
- References
- 84
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 3 · 2017: 5 · 2016: 9 · 2015: 6 · 2014: 9 · 2013: 14 · 2012: 8
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- eCommons - AKU (Aga Khan University) (submittedVersion)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- anxiety assessment, novel environment, predator scent, home cage, anxiolytics, diazepam, chlordiazepoxide, propranolol, buspirone, desmethylimipramine, haloperidol, amphetamine, mice
- MeSH terms
- Animals, Anxiety, Conflict, Psychological, Environment, Ethology, Feeding Behavior, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Models, Psychological, Reaction Time, Stress, Psychological, Anti-Anxiety Agents, Reproducibility of Results, Mice
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