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Realistic expectations of prepulse inhibition in translational models for schizophrenia research
Open accessAbstract
Introduction Under specific conditions, a weak lead stimulus, or "prepulse", can inhibit the startling effects of a subsequent intense abrupt stimulus. This startle-inhibiting effect of the prepulse, termed "prepulse inhibition" (PPI), is widely used in translational models to understand the biology of brainbased inhibitory mechanisms and their deficiency in neuropsychiatric disorders. In 1981, four published reports with "prepulse inhibition" as an index term were listed on Medline; over the past 5 years, new published Medline reports with "prepulse inhibition" as an index term have appeared at a rate exceeding once every 2.7 days (n=678). Most of these reports focus on the use of PPI in translational models of impaired sensorimotor gating in schizophrenia. This rapid expansion and broad application of PPI as a tool for understanding schizophrenia has, at times, outpaced critical thinking and falsifiable hypotheses about the relative strengths vs. limitations of this measure.Objectives This review enumerates the realistic expectations for PPI in translational models for schizophrenia research, and provides cautionary notes for the future applications of this important research tool.Conclusion In humans, PPI is not "diagnostic"; levels of PPI do not predict clinical course, specific symptoms, or individual medication responses. In preclinical studies, PPI is valuable for evaluating models or model organisms relevant to schizophrenia, "mapping" neural substrates of deficient PPI in schizophrenia, and advancing the discovery and development of novel therapeutics. Across species, PPI is a reliable, robust quantitative phenotype that is useful for probing the neurobiology and genetics of gating deficits in schizophrenia.
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“normalizing PPI deficits in rodent models has enabled drug discovery for potential antipsychotic medications [371], some of which have proven successful in treating schizophrenia [368,372].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [368]
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Metadata
- Authors
- Swerdlow, N. R., Weber, M., Qu, Y., Light, G. A., & Braff, D. L.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Swerdlow, Neal R.
- Venue
- Psychopharmacology
- Published
- 2008-06-21
- Volume
- 199
- Issue
- 3
- Pages
- 331-388
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC2771731
- OpenAlex
- W2062472783
- Cited by
- 529
- References
- 478
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 13 · 2023: 18 · 2022: 19 · 2021: 23 · 2020: 31 · 2019: 21 · 2018: 23 · 2017: 30 · 2016: 38 · 2015: 42 · 2014: 31 · 2013: 51 · 2012: 38
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- National Alliance for Research on Schizophrenia and Depression
- ACADIA Pharmaceuticals
- Allergan
- Pfizer Pharmaceuticals
- National Institute of Mental Health (MH 53484, MH68366, R01MH069589, MH65571, MH69589, MH42228, R01MH068366, R37MH042228, R01MH053484, R01MH042228, R01MH059803, MH 79777, MH 58903, R01MH065571, R01MH079777)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- prepulse inhibition, schizophrenia, sensorimotor gating, translational model, animal models of schizophrenia, startle response, inhibition mechanism, preclinical drug screening, quantitative phenotypes, model organisms
- MeSH terms
- Animals, Disease Models, Animal, Humans, Models, Psychological, Schizophrenia, Schizophrenic Psychology, Reflex, Startle, Antipsychotic Agents
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