Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.
Celia Kjærby, Brian V Broberg, Uffe Kristiansen, Nils Ole Dalby
Cerebral Cortex September 2014 DOI: 10.1093/cercor/bht109 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study (whole-cell patch-clamp electrophysiology in rats) Peer reviewed |
|---|---|
| Population | Adult rats treated with phencyclidine during the second postnatal week |
| Intervention | Phencyclidine (PCP) |
| Duration | 3 days during the second postnatal week |
| Keywords | Nmda receptor antagonist Development Electrophysiology Frontal cortex Interneuron |
| Key findings | Early postnatal PCP treatment reduced miniature inhibitory postsynaptic current frequency by 22% in layer II/III, but not layer V, prefrontal pyramidal neurons, and diminished both sensitivity to a GAT-1 inhibitor and currents through δ-subunit-containing GABAA receptors. The authors argue these findings support the hypothesis that developmental NMDA receptor hypofunction impairs interneuron function in adulthood. |
Abstract
A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life.
Citations in the library
Cited by 5
- Reinforcement learning deficits exhibited by postnatal PCP-treated rats enable deep neural network classification. Neuropsychopharmacology August 2023
- Postnatal Phencyclidine-Induced Deficits in Decision Making Are Ameliorated by Optogenetic Inhibition of Ventromedial Orbitofrontal Cortical Glutamate Neurons Biological Psychiatry Global Open Science August 1, 2023
- TPA-023 attenuates subchronic phencyclidine-induced declarative and reversal learning deficits via GABAA receptor agonist mechanism: possible therapeutic target for cognitive deficit in schizophrenia. Neuropsychopharmacology November 2018
- Down-Regulation of Hippocampal Genes Regulating Dopaminergic, GABAergic, and Glutamatergic Function Following Combined Neonatal Phencyclidine and Post-Weaning Social Isolation of Rats as a Neurodevelopmental Model for Schizophrenia. The International Journal of Neuropsychopharmacology November 2016
- Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus. Neuropharmacology January 2016
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