Cited by 864Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

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Behavioural and neurochemical effects of post-weaning social isolation in rodents—Relevance to developmental neuropsychiatric disorders

Fone, Kevin C.F., Porkess, M. Veronica·2008·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2008.03.003

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Abstract

Exposing mammals to early-life adverse events, including maternal separation or social isolation, profoundly affects brain development and adult behaviour and may contribute to the occurrence of psychiatric disorders, such as depression and schizophrenia in genetically predisposed humans. The molecular mechanisms underlying these environmentally induced developmental adaptations are unclear and best evaluated in animal paradigms with translational salience. Rearing rat pups from weaning in isolation, to prevent social contact with conspecifics, produces reproducible, long-term changes including; neophobia, impaired sensorimotor gating, aggression, cognitive rigidity, reduced prefrontal cortical volume and decreased cortical and hippocampal synaptic plasticity. These alterations are associated with hyperfunction of mesolimbic dopaminergic systems, enhanced presynaptic dopamine (DA) and serotonergic (5-HT) function in the nucleus accumbens (NAcc), hypofunction of mesocortical DA and attenuated 5-HT function in the prefrontal cortex and hippocampus. These behavioural, morphological and neurochemical abnormalities, as reviewed herein, strongly resemble core features of schizophrenia. Therefore unravelling the mechanisms that trigger these sequelae will improve our knowledge of the aetiology of neurodevelopmental psychiatric disorders, enable identification of longitudinal biomarkers of dysfunction and permit predictive screening for novel compounds with potential antipsychotic efficacy.

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Authors: Fone, K. C. F., & Porkess, M. V.
Affiliations: University of Nottingham (GB)
Corresponding author: Fone, Kevin C.F.
ORCID: Fone, Kevin C.F.
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2008-08
Volume: 32
Issue: 6
Pages: 1087-1102
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2008.03.003
OpenAlex: W2019243277
Cited by: 864
References: 208
Citations by year: 2026: 28 · 2025: 34 · 2024: 37 · 2023: 46 · 2022: 41 · 2021: 64 · 2020: 51 · 2019: 47 · 2018: 41 · 2017: 62 · 2016: 50 · 2015: 71 · 2014: 55 · 2013: 57 · 2012: 54
FWCI: 5.34
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (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 › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: post-weaning social isolation, maternal separation, childhood adversity, schizophrenia, depression, neophobia, sensorimotor gating, aggression, synaptic plasticity, mesolimbic dopamine system, mesocortical dopamine, nucleus accumbens, serotonin, prefrontal cortex, hippocampus, brain development, biomarkers
MeSH terms: Animals, Animals, Newborn, Behavior, Animal, Brain Chemistry, Child, Developmental Disabilities, Disease Models, Animal, Humans, Rodentia, Social Isolation

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Behavioural and neurochemical effects of post-weaning social isolation in rodents—Relevance to developmental neuropsychiatric disorders

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