Cited by 107Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Adolescent Maturation of Cortical Dopamine

O’Donnell, Patricio·2010·Neurotoxicity Research

Abstract

Dopamine is a critical modulator of prefrontal cortical function, and it is known to be dysfunctional in schizophrenia. Current hypotheses on schizophrenia highlight developmental aspects and genetic predisposition for the disease; yet, symptom onset typically occurs during adolescence. Several aspects of prefrontal cortical circuits and their modulation by dopamine mature postnatally, as late as during adolescence. Here we review studies assessing the postnatal trajectory of dopamine control of GABA interneurons, a neuronal population that has been long suspected to be critical for schizophrenia pathophysiology. Dopamine modulation of fast-spiking interneurons changes dramatically during adolescence (postnatal day 45-50 in rats) with D2 agonists switching from being mildly inhibitory in prepubertal rats to strongly excitatory in young adult rats. In vivo recordings in adult rats reveal that deep-layer pyramidal neurons respond to endogenous DA release with suppression of firing while interneurons are activated. In adult rats with a neonatal ventral hippocampal lesion (NVHL), an extensively studied developmental model of schizophrenia, the maturation in the D2 modulation of interneuron physiology fails to occur, rendering a disinhibited prefrontal cortex. Abnormal interneuron maturation may therefore impair cognitive function in the adult animal.

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Crossref · 10.1007/s12640-010-9157-3

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Authors
O’Donnell, P.
Affiliations
University of Maryland, Baltimore (US)
Corresponding author
O’Donnell, Patricio
Venue
Neurotoxicity Research
Published
2010-02-12
Volume
18
Issue
3-4
Pages
306-312
ISSN
  • 1029-8428 (ISSN-L)
  • 1476-3524
OpenAlex
W1964516189
Cited by
107
References
64
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 21 · 2012: 5
FWCI
1.70
Type
journal article
Language
en
Open access
closed
Locations
  • Neurotoxicity Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (MH57683)
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
dopamine, adolescent brain development, prefrontal cortex, GABAergic interneurons, fast-spiking interneurons, dopamine D2 receptor, schizophrenia, pyramidal neurons, endogenous dopamine release, cognitive function
MeSH terms
Action Potentials, Adolescent, Animals, Dopamine, Humans, Nerve Net, Schizophrenia, Schizophrenic Psychology, Prefrontal Cortex

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