Phencyclidine Disrupts the Auditory Steady State Response in Rats

Area of Science:

• Neuroscience
• Psychopharmacology
• Auditory Neuroscience

Background:

• Auditory Steady-State Responses (ASSRs) are often reduced in schizophrenia (SZ), particularly at 40 Hz.
• This gamma frequency ASSR deficit is linked to N-methyl-D-aspartate receptor (NMDAR) hypofunction.
• Phencyclidine (PCP) is a known NMDAR antagonist used to model SZ symptoms.

Purpose of the Study:

• To investigate if the NMDAR antagonist phencyclidine (PCP) induces similar ASSR deficits in rats as observed in schizophrenia.
• To examine the dose-dependent and schedule-dependent effects of PCP on ASSRs in rats.

Main Methods:

• Electroencephalogram (EEG) recordings of ASSRs in awake rats to click trains at various frequencies (10-55 Hz).
• Measurement of ASSR Mean Power (MP) and Phase Locking Factor (PLF) at auditory cortex and vertex electrode sites.
• Administration of acute subcutaneous PCP doses (1.0-4.0 mg/kg) and subchronic continuous administration (5 mg/kg/day).

Main Results:

• Acute PCP administration increased low-frequency (below 50 Hz) PLF and MP at the auditory cortex, while decreasing high-frequency (>40 Hz) responses.
• Effects were more pronounced at higher PCP doses and less consistent at the vertex site.
• Subchronic PCP administration did not produce consistent effects on ASSRs.

Conclusions:

• Acute PCP administration in rats mimics some ASSR alterations seen in schizophrenia, suggesting NMDAR involvement.
• ASSRs are sensitive to NMDAR antagonists, but their utility as a biomarker may depend on PCP dose and administration schedule.
• Findings highlight the complexity of using ASSRs as a cross-species biomarker for NMDAR hypofunction.