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

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Adolescent Maturation of Cortical Dopamine

O’Donnell, Patricio·2010·Neurotoxicity Research

DOI 10.1007/s12640-010-9157-3

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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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Authors: O’Donnell, P.
Affiliations: University of Maryland, Baltimore (US)
Corresponding author: O’Donnell, Patricio
ORCID: O’Donnell, Patricio
Venue: Neurotoxicity Research
Publisher: Springer Science and Business Media LLC
Published: 2010-02-12
Volume: 18
Issue: 3-4
Pages: 306-312
ISSN: 1029-8428 (ISSN-L)
1476-3524
DOI: 10.1007/s12640-010-9157-3
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
Licence: www.springer.com/tdm (tdm)
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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