Cited by 161Anesthesia and Neurotoxicity ResearchSchizophrenia research and treatmentNeuroscience and Neuropharmacology Research

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Postnatal Phencyclidine Administration Selectively Reduces Adult Cortical Parvalbumin-Containing Interneurons

Wang, Cheng Z, Yang, San F, Xia, Yan, Johnson, Kenneth M·2008·Neuropsychopharmacology

DOI 10.1038/sj.npp.1301647

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Abstract

Transient postnatal NMDA receptor blockade by phencyclidine (PCP), ketamine, or MK-801 induces developmental neuroapoptosis and adult behavioral deficits, which resemble abnormal human behaviors typically present in schizophrenia. This study tested the hypothesis that PCP-induced developmental apoptosis causes a specific deficit of GABAergic interneurons containing parvalbumin (PV), calretinin (CR), or calbindin (CB). Young adult (PND56) rats that were given a single dose of PCP (10 mg/kg) on PND7 exhibited no densitometric change of either CR or CB neurons in any brain region studied, but demonstrated a selective deficit of PV-containing neurons in the superficial layers (II-IV) of the primary somatosensory (S1), motor (M), and retrosplenial cortices, but not in the striatum (CPu) or hippocampus. Further, CR and CB neurons, which were expressed at the time of PCP administration, showed no colocalization with cellular markers of apoptosis (terminal dUTP nick-end labeling (TUNEL) of broken DNA or cleaved caspase-3), indicating that CR- and CB-containing neurons were protected from the toxic effect of PCP and survived into adulthood. This suggests that the deletion of PV neurons occurred during development, but cleaved caspase-3 showed no colocalization with BrdU, a specific marker of S-phase proliferation. These data suggest that the loss of PV-containing neurons was not due to an effect of PCP on proliferating neurons, but rather an effect on post-mitotic neurons. The developmental dependence and neuronal specificity of this effect of PCP provides further evidence that this model may be valuable in exploring the pathophysiology of schizophrenia.

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Copyright Page
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Preface
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Authors: Wang, C. Z., Yang, S. F., Xia, Y., & Johnson, K. M.
Affiliations: The University of Texas Medical Branch at Galveston (US)
Corresponding author: Wang, Cheng Z
Johnson, Kenneth M
ORCID: Xia, Yan
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2007-12-05
Volume: 33
Issue: 10
Pages: 2442-2455
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1301647
OpenAlex: W2026782090
Cited by: 161
References: 110
Citations by year: 2026: 1 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 6 · 2015: 13 · 2014: 13 · 2013: 11 · 2012: 7
FWCI: 5.48
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Health and Human Services
University of Texas Medical Branch
National Institutes of Health (5r01mh063871-04)
National Institute of Mental Health (MH63871)
National Institute on Drug Abuse (DA 02073, R01DA002073)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: phencyclidine, NMDA receptor blockade, parvalbumin interneurons, calretinin, calbindin, GABAergic interneurons, schizophrenia model, postnatal drug exposure, caspase-3, TUNEL, somatosensory cortex, motor cortex, retrosplenial cortex
MeSH terms: Animals, Animals, Newborn, Bromodeoxyuridine, Cell Count, Cell Survival, Cerebral Cortex, Disease Models, Animal, Female, Interneurons, Male, Parvalbumins, Phencyclidine, Schizophrenia, Time, Rats, Sprague-Dawley, Apoptosis, Excitatory Amino Acid Antagonists, Cell Proliferation, Rats, Caspase 3, Calbindins, S100 Calcium Binding Protein G, Calbindin 2

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Postnatal Phencyclidine Administration Selectively Reduces Adult Cortical Parvalbumin-Containing Interneurons

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