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Postpubertal Emergence of Hyperresponsiveness to Stress and to Amphetamine after Neonatal Excitotoxic Hippocampal Damage: A Potential Animal Model of Schizophrenia
Abstract
The constellation of major phenomena associated with schizophrenia (e.g., postpubertal onset, congenital hippocampal area damage, cortical functional deficits, limbic dopamine (DA) dysregulation, and vulnerability to stress) have been difficult to explain with a unitary animal model. Although it has been shown that rats develop increased mesolimbic DA transmission and reduced cortical DA turnover following adult excitotoxic lesions of the ventral hippocampus (VH), the implications of early developmental VH lesions are not known. To determine the developmental sequelae of such changes, we produced ibotenic acid lesions of the ventral hippocampal formation in rats on the 7th day after birth (PD7). Motor activity in a novel environment, after saline injection and after d-amphetamine administration were similar in control and lesioned rats at PD35. However, in early adulthood, at PD56, animals with the hippocampal lesion were hyperactive in each of these conditions. The emergence of the hyperactivity at PD56 could be prevented by pretreatment with haloperidol. Moreover, rats lesioned as neonates, in contrast to a similar lesion induced in adult animals, were also hyperresponsive to stress evaluated with a swim test. This latter effect is analogous to that seen after adult lesions of the medial prefrontal cortex, rather than after adult lesions of VH, suggesting that the neonatal VH lesion may affect functional development of the medial prefrontal cortex. These results demonstrate…
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“These are primarily based on pharmacological lesions of the developing hippocampus, such as the prenatal exposure to methylazoxymethanol acetate (MAM) and the neonatal ventral hippocampal lesion (NVHL) models 55,56 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [55]
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“Both models reproduce some of the defects observed in schizophrenia, including functional deficits in PV+ fast spiking interneurons.”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [55]
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Metadata
- Authors
- Lipska, B. K., Jaskiw, G. E., & Weinberger, D. R.
- Affiliations
- National Institute of Mental Health (US)
- University Hospitals of Cleveland (US)
- Venue
- Neuropsychopharmacology
- Published
- 1993-08
- Volume
- 9
- Issue
- 1
- Pages
- 67-75
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2012245779
- Cited by
- 697
- References
- 34
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 2 · 2023: 5 · 2022: 10 · 2021: 14 · 2020: 12 · 2019: 10 · 2018: 8 · 2017: 13 · 2016: 19 · 2015: 22 · 2014: 26 · 2013: 19 · 2012: 30
- FWCI
- 21.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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
- schizophrenia, animal models of schizophrenia, ventral hippocampus, ibotenic acid, dopamine dysregulation, haloperidol
- MeSH terms
- Animals, Animals, Newborn, Dextroamphetamine, Disease Models, Animal, Female, Haloperidol, Hippocampus, Ibotenic Acid, Motor Activity, Pregnancy, Schizophrenia, Stress, Psychological, Swimming, Rats, Sprague-Dawley, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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