Cited by 698Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Postpubertal Emergence of Hyperresponsiveness to Stress and to Amphetamine after Neonatal Excitotoxic Hippocampal Damage: A Potential Animal Model of Schizophrenia

Lipska, Barbara K., Jaskiw, George E., Weinberger, Daniel R.·1993·Neuropsychopharmacology

DOI 10.1038/npp.1993.44

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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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Authors: Lipska, B. K., Jaskiw, G. E., & Weinberger, D. R.
Affiliations: National Institute of Mental Health (US)
University Hospitals of Cleveland (US)
ORCID: Jaskiw, George E.
Weinberger, Daniel R.
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 1993-08
Volume: 9
Issue: 1
Pages: 67-75
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/npp.1993.44
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

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Postpubertal Emergence of Hyperresponsiveness to Stress and to Amphetamine after Neonatal Excitotoxic Hippocampal Damage: A Potential Animal Model of Schizophrenia

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