Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats

Ashley M. Schnakenberg Martin, Brian O'Donnell, James B. Millward, Jenifer Vohs, Emma Leishman, Amanda R. Bolbecker, Olga Rass, Sandra Morzorati

Research output: Contribution to journalArticle

Abstract

Background/Aims: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. Methods: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. Results: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. Conclusions: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalNeuropsychobiology
DOIs
StateAccepted/In press - Oct 24 2017

Fingerprint

Phencyclidine
Auditory Cortex
Electroencephalography
N-Methyl-D-Aspartate Receptors
Evoked Potentials
Schizophrenia
Power (Psychology)
Biomarkers

Keywords

  • Auditory event-related potential
  • N-methyl-D-aspartate receptor antagonism
  • Neural synchrony
  • Phencyclidine
  • Rat model
  • Schizophrenia

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats. / Schnakenberg Martin, Ashley M.; O'Donnell, Brian; Millward, James B.; Vohs, Jenifer; Leishman, Emma; Bolbecker, Amanda R.; Rass, Olga; Morzorati, Sandra.

In: Neuropsychobiology, 24.10.2017, p. 53-62.

Research output: Contribution to journalArticle

Schnakenberg Martin, Ashley M. ; O'Donnell, Brian ; Millward, James B. ; Vohs, Jenifer ; Leishman, Emma ; Bolbecker, Amanda R. ; Rass, Olga ; Morzorati, Sandra. / Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats. In: Neuropsychobiology. 2017 ; pp. 53-62.
@article{12974c6718114ea5a785298f9468dc17,
title = "Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats",
abstract = "Background/Aims: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. Methods: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. Results: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. Conclusions: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.",
keywords = "Auditory event-related potential, N-methyl-D-aspartate receptor antagonism, Neural synchrony, Phencyclidine, Rat model, Schizophrenia",
author = "{Schnakenberg Martin}, {Ashley M.} and Brian O'Donnell and Millward, {James B.} and Jenifer Vohs and Emma Leishman and Bolbecker, {Amanda R.} and Olga Rass and Sandra Morzorati",
year = "2017",
month = "10",
day = "24",
doi = "10.1159/000480511",
language = "English (US)",
pages = "53--62",
journal = "Neuropsychobiology",
issn = "0302-282X",
publisher = "S. Karger AG",

}

TY - JOUR

T1 - Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats

AU - Schnakenberg Martin, Ashley M.

AU - O'Donnell, Brian

AU - Millward, James B.

AU - Vohs, Jenifer

AU - Leishman, Emma

AU - Bolbecker, Amanda R.

AU - Rass, Olga

AU - Morzorati, Sandra

PY - 2017/10/24

Y1 - 2017/10/24

N2 - Background/Aims: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. Methods: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. Results: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. Conclusions: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.

AB - Background/Aims: The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. Methods: Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. Results: Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. Conclusions: Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders.

KW - Auditory event-related potential

KW - N-methyl-D-aspartate receptor antagonism

KW - Neural synchrony

KW - Phencyclidine

KW - Rat model

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85032394930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032394930&partnerID=8YFLogxK

U2 - 10.1159/000480511

DO - 10.1159/000480511

M3 - Article

SP - 53

EP - 62

JO - Neuropsychobiology

JF - Neuropsychobiology

SN - 0302-282X

ER -