Cited by 105Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorTryptophan and brain disorders

Peripubertal Diazepam Administration Prevents the Emergence of Dopamine System Hyperresponsivity in the MAM Developmental Disruption Model of Schizophrenia

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Du, Yijuan, Grace, Anthony A·2013·Neuropsychopharmacology

Abstract

Schizophrenia is believed to arise from an interaction of genetic predisposition and adverse environmental factors, with stress being a primary variable. We propose that alleviating anxiety produced in response to stress during a sensitive developmental period may circumvent the dopamine (DA) system alterations that may correspond to psychosis in adults. This was tested in a developmental rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM). MAM administration leads to a hyperdopaminergic state consisting of an increase in the number of DA neurons firing spontaneously, which correlates with an increased behavioral response to amphetamine. MAM-treated rats exhibited a heightened level of anxiety during adolescence. Peripubertal administration of the antianxiety agent diazepam was found to prevent the increase in DA neuron activity and blunt the behavioral hyperresponsivity to amphetamine in these rats. These data suggest that the pathophysiological factors leading to the onset of psychosis in early adulthood may be circumvented by controlling the response to stress during the peripubertal period.

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Crossref · 10.1038/npp.2013.101

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  • Reducing stress sensitivity in juvenile MAM-treated rats with benzodiazepines prevents the abnormal increase in the activity of dopaminergic neurons and reduces hyperlocomotion in adult rats.

    “Consistent with this view, reducing stress sensitivity in juvenile MAM-treated rats with benzodiazepines prevents the abnormal increase in the activity of dopaminergic neurons and reduces hyperlocomotion in adult rats 71 .”

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Authors
Du, Y., & Grace, A. A.
Affiliations
University of Pittsburgh (US)
Corresponding author
Du, Yijuan
Venue
Neuropsychopharmacology
Published
2013-04-23
Volume
38
Issue
10
Pages
1881-1888
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
OpenAlex
W1970236655
Cited by
105
References
56
Citations by year
2026: 5 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 8 · 2020: 10 · 2019: 10 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 6 · 2014: 5 · 2013: 4
FWCI
6.16
Type
journal article
Language
en
Open access
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (2r01mh057440-26a1)
  • National Institute of Mental Health (MH-57440, R01-MH057440, R37MH057440)
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 › Biological Psychiatry › Tryptophan and brain disorders
Keywords
schizophrenia, methylazoxymethanol acetate, diazepam, peripubertal period, anxiety, stress, amphetamine response, psychosis prevention, rat model
MeSH terms
Amphetamine, Animals, Anxiety, Diazepam, Female, Male, Methylazoxymethanol Acetate, Motor Activity, Pregnancy, Prenatal Exposure Delayed Effects, Schizophrenia, Ventral Tegmental Area, Maze Learning, Rats, Dopaminergic Neurons, Central Nervous System Sensitization

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