Effects of NMDA and GABA-A Receptor Antagonism on Auditory Steady-State Synchronization in Awake Behaving Rats

• Published in: The international journal of neuropsychopharmacology Vol. 18; no. 7; p. pyu118
• Main Authors: Sullivan, Elyse M., Timi, Patricia, Hong, L. Elliot, O’Donnell, Patricio
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-05-2015
• Subjects: Acoustic Stimulation - methods; Animals; Auditory Cortex - drug effects; Auditory Cortex - physiology; Auditory Perception - drug effects; Auditory Perception - physiology; Dizocilpine Maleate - administration & dosage; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Electroencephalography; Evoked Potentials, Auditory - drug effects; Evoked Potentials, Auditory - physiology; Excitatory Amino Acid Antagonists - pharmacology; GABA-A Receptor Antagonists - pharmacology; Hippocampus - drug effects; Hippocampus - physiology; Male; Picrotoxin - administration & dosage; Picrotoxin - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Synaptic Transmission - drug effects; Wakefulness - physiology; GABA; freely moving electrophysiology; EEG; NMDA receptor antagonist; ASSR
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1093/ijnp/pyu118

Background:
The auditory steady-state response, which measures the ability of neural ensembles to entrain to rhythmic auditory stimuli, has been used in human electroencephalogram studies to assess sensory processing and electrical oscillatory deficits. Patients with schizophrenia show a deficit in auditory steady-state response at 40 Hz, and therefore this may be a useful biomarker to study this disorder.
Methods:
We used auditory steady-state response recordings from the primary auditory cortex, hippocampus, and vertex electroencephalogram sites in awake behaving rats to determine whether pharmacological impairment of excitatory or inhibitory neurotransmission mimics auditory steady-state response abnormalities in schizophrenia.
Results:
We found the most robust response to auditory stimuli in the primary auditory cortex, in line with previous studies suggesting this region is the primary generator of the auditory steady-state response in humans. Acute MK-801 (0.1mg/kg i.p.) increased primary auditory cortex intertrial coherence during auditory steady-state response at 20 and 40 Hz. Chronic MK-801 (21-day exposure at this daily dose) had no significant effect on 40-Hz auditory steady-state response. Furthermore, we found no effect of acute or chronic picrotoxin (a GABA-A antagonist) on intertrial coherence.
Conclusions:
Our data indicate that acute N-methyl-d-aspartate receptor antagonism increases synchronous activity in the primary auditory cortex in a frequency-specific manner, supporting the widely held view that acute N-methyl-d-aspartate antagonism augments gamma oscillations. Thus, rodent auditory steady-state response could be a valuable method to study the cortical ability to support synchronous activity at specific frequencies.