Post-Pubertal Disruption of Medial Prefrontal Cortical Dopamine–Glutamate Interactions in a Developmental Animal Model of Schizophrenia
Open accessAbstract
Background A neonatal ventral hippocampal lesion (NVHL) induces behavioral and physiological anomalies mimicking pathophysiological changes of schizophrenia. Because prefrontal cortical (PFC) pyramidal neurons recorded from adult NVHL rats exhibit abnormal responses to activation of the mesocortical dopaminergic (DA) system, we explored whether these changes are due to an altered DA modulation of pyramidal neurons.Methods Whole-cell recordings were used to examine the effects of DA and glutamate agonists on cell excitability in brain slices obtained from pre- (postnatal day [PD] 28-35) and post-pubertal (PD > 61) sham and NVHL animals.Results N-methyl d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA), and the D(1) agonist SKF38393 increased excitability of deep layer pyramidal neurons in a concentration-dependent manner. The opposite effect was observed with the D(2) agonist quinpirole. The effects of NMDA (but not AMPA) and SKF38393 on cell excitability were significantly higher in slices from NVHL animals, whereas quinpirole decrease of cell excitability was reduced. These differences were not observed in slices from pre-pubertal rats, suggesting that PFC DA and glutamatergic systems become altered after puberty in NVHL rats.Conclusions A disruption of PFC dopamine-glutamate interactions might emerge after puberty in brains with an early postnatal deficit in hippocampal inputs, and this disruption could contribute to the manifestation of schizophrenia-like symptoms.
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Recordings in brain slices revealed increased excitability of pyramidal neurons and a deficient activation of fast-spiking GABA interneurons by D2 agonists in the PFC of NVHL rats.
“Recordings in brain slices revealed increased excitability of pyramidal neurons 52 and a deficient activation of fast-spiking GABA interneurons by D 2 agonists 53 in the PFC of NVHL rats.”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [52]
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References 42 · Cited by 132
- Authors
- Tseng, K.-Y., Lewis, B. L., Lipska, B. K., & O’Donnell, P.
- Affiliations
- Rosalind Franklin University of Medicine and Science (US)
- Albany Medical College (US)
- National Institute of Mental Health (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- O’Donnell, Patricio
- ORCID
- O’Donnell, Patricio
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 62
- Issue
- 7
- Pages
- 730-738
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2204086
- OpenAlex
- W1966465143
- Cited by
- 132
- References
- 42
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 3 · 2015: 8 · 2014: 6 · 2013: 11 · 2012: 12
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH57683, R56MH057683, R01MH057683)
- 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, dopamine-glutamate interaction, medial prefrontal cortex, pyramidal neurons, excitability, NMDA receptor, AMPA receptors, dopamine D1 receptor, dopamine D2 receptor, quinpirole, SKF 38393, ventral hippocampus, animal models of schizophrenia
- MeSH terms
- Animals, Animals, Newborn, Disease Models, Animal, Dopamine, Electrophysiology, Female, Hippocampus, Neurons, Pregnancy, Schizophrenia, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, N-Methylaspartate, Rats, Sprague-Dawley, Prefrontal Cortex, Receptors, Dopamine D1, Receptors, Dopamine D2, Pyramidal Cells, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Patch-Clamp Techniques, Dopamine Agonists, Excitatory Amino Acid Agonists, Glutamic Acid, Rats
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