Phencyclidine Disrupts the Auditory Steady State Response in Rats
Authors: Brian F O&#x27;Donnell
Emma Leishman
James B Millward
Giri P Krishnan
Olga Rass
Sandra L Morzorati
Amanda R Bolbecker
Jenifer L Vohs
Journal: PLoS ONE (2015)
Discipline: Multidisciplinary
Keywords: Auditory Steady-State Response; ASSR; Schizophrenia; N-methyl-D-aspartate receptor; NMDAR
Affiliations: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States of America., Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States of America; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States of America; Larue D. Carter Memorial Hospital, Indianapolis, Indiana, United States of America., Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States of America., University of California Riverside, Riverside, CA, United States of America.

Abstract:  The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (&gt; 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule. 

Retracted: No

PubPeer comments:
 * Antipsychotic drugs such as clozapine and haloperidol suppress spontaneous gamma power in mice [42] * The cited paper for this statement doesn t show anything like this. * 42. Ehrlichman RS, Gandal MJ, Maxwell CR, Lazarewicz MT, Finkel LH, Contreras D, et al. N-methyl-d-aspartic acid receptor antagonist-induced frequency oscillations in mice recreate the pattern of electrophysiological deficits in schizophrenia. Neuroscience. 2009;158(2):705u201312. Epub 2008 11 19. pmid:19015010. * The paper in fact shows that only Ketamine shows a significant effect on baseline gamma but no other antipsychotic. They didn t even try clozapine in this study. The authors should have been more careful with their citations. , 
 #1 Thank you for pointing out this mis-citation. I am not sure how it occurred in the course of multiple revisions, but we will redouble our efforts at accuracy. with appreciation, Brian ODonnell ,