Animal models of neuropsychiatric disorders

Nestler, Eric J; Hyman, Steven E

doi:10.1038/nn.2647

Cited by 2,023Neurotransmitter Receptor Influence on BehaviorSchizophrenia research and treatmentAnimal testing and alternatives

Animal models of neuropsychiatric disorders

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Nestler, Eric J, Hyman, Steven E·2010·Nature Neuroscience

DOI 10.1038/nn.2647PMC PMC3750731

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Abstract

Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression and bipolar disorder. We argue for areas of focus that might increase the likelihood of creating more useful models, at least for some disorders, and for explicit guidelines when animal models are reported.

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There is a paucity of animal studies of bipolar disorder mainly because there are no animal models that satisfy the validity criteria for modeling this complex multifactorial disorder.
“There is a paucity of animal studies of BD mainly because there are no animal models that satisfy the validity criteria for modeling this complex multifactorial disorder130–133.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [132]
The 'Animal models of bipolar disorder' section says researchers have struggled to model mania and have not developed rodent models with spontaneously alternating manic- and depressive-like episodes. The 'Generating and validating' section identifies weaknesses in existing models, but also says some meet face and predictive validity criteria. The paper does not establish a paucity of animal studies or attribute one mainly to a complete absence of models meeting validity criteria. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Chronic unpredictable stress, restraint stress or foot-shock stress followed by behavioral measures of anhedonia or behavioral despair are often responsive to acute antidepressant treatment and do not address the multiple validities necessary for an effective animal model of depression.
“These include chronic unpredictable stress, restraint stress or foot-shock stress, followed by behavioral measures of anhedonia (e.g., sucrose preference) or behavioral despair (e.g., forced swim test and tail suspension test), which are often responsive to acute antidepressant treatment and do not address the multiple validities necessary for an effective animal model of depression4.”
From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [4]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
For complex psychiatric disorders with largely unknown genetic etiologies, environmental insults, specific pathologies, or biomarkers, the building of animal models with high construct validity has not yet been possible.
“However, for complex psychiatric disorders with largely unknown genetic etiologies, environmental insults, specific pathologies, or biomarkers, the building of animal models with high construct validity has not yet been possible [94].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [94]
Mice subjected to chronic social defeat stress (CSDS) develop depression-like symptoms.
“Mice subjected to chronic social defeat stress (CSDS) develop depression-like symptoms [134,135]”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [134]
Stress-induced behavioral phenotypes are reversed by chronic, but not acute antidepressant treatment, and are thus posited to have both face and predictive validity.
“The stress-induced behavioral phenotypes are reversed by chronic, but not acute antidepressant treatment, and are thus posited to have both face and predictive validity [8].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [8]

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[71]Welch JM Cortico-striatal synaptic defects and OCD-like behaviors in Sapap3-mutant mice Nature 448 894 901 2007 17713528 PMC2442572

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“social avoidance and anhedonia (reduced sensitivity to reward) (8,9).”
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Cortical Control of Affective Networks
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Authors: Nestler, E. J., & Hyman, S. E.
Affiliations: Icahn School of Medicine at Mount Sinai (US)
Harvard University (US)
Corresponding author: Nestler, Eric J
ORCID: Nestler, Eric J
Hyman, Steven E
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2010-09-27
Volume: 13
Issue: 10
Pages: 1161-1169
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.2647
PMC: PMC3750731
OpenAlex: W2007816528
Cited by: 2,023
References: 72
Citations by year: 2026: 81 · 2025: 109 · 2024: 101 · 2023: 103 · 2022: 114 · 2021: 144 · 2020: 146 · 2019: 160 · 2018: 135 · 2017: 151 · 2016: 131 · 2015: 168 · 2014: 140 · 2013: 109 · 2012: 109
FWCI: 9.70
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (P50MH090963, R01MH051399, P50MH066172)
National Institute on Drug Abuse (R01DA014133)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
Keywords: animal models of psychiatric disorders, schizophrenia, bipolar disorder, depression, neuropsychiatric disorders, model validation, reporting guidelines, biomarkers, treatment development, pathophysiology
MeSH terms: Animals, Mental Disorders, Disease Models, Animal, Humans, Nerve Tissue Proteins, Reproducibility of Results, Neurotransmitter Agents

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