title: Phencyclidine Disrupts the Auditory Steady State Response in Rats.
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 (> 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.
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States of America.
authors.forename: Emma
authors.initials: E
authors.lastname: Leishman
authors.affiliation: 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.
authors.forename: Brian F
authors.initials: BF
authors.lastname: O'Donnell
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States of America.
authors.forename: James B
authors.initials: JB
authors.lastname: Millward
authors.affiliation: 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.
authors.forename: Jenifer L
authors.initials: JL
authors.lastname: Vohs
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States of America.
authors.forename: Olga
authors.initials: O
authors.lastname: Rass
authors.affiliation: University of California Riverside, Riverside, CA, United States of America.
authors.forename: Giri P
authors.initials: GP
authors.lastname: Krishnan
authors.affiliation: 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.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Bolbecker
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States of America.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Morzorati
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001303:Auditory Cortex / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000473:pathology; D003198:Computer Simulation; D004566:Electrodes; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000737:chemistry; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D008297:Male; D010622:Phencyclidine / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012559:Schizophrenia / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D010622:Phencyclidine