Effects of phencyclidine on auditory gating in the rat hippocampus and the medial prefrontal cortex.
Sensory gating can be assessed using an auditory conditioning (C)-test (T) paradigm which measures the reduction in the auditory-evoked response produced by a test stimulus following a conditioning stimulus. Schizophrenic patients demonstrate absence of gating while dysfunction in glutamatergic neurotransmission is implicated in the pathophysiology of schizophrenia. This study examined the effect of the glutamate receptor antagonist, phencyclidine (PCP) on auditory gating in the CA3 region and dentate gyrus (DG) of rat hippocampus and medial prefrontal cortex (mPFC). Local field potential (LFP) activity was recorded simultaneously from CA3, DG and mPFC in isoflurane anaesthetised Lister hooded rats using in vivo electrophysiology. Paired auditory stimuli were presented binaurally over 128 trials. The effect of PCP (1 mg/kg, i.p.) on gating of the N2 LFP wave was assessed as the test:conditioning response amplitude ratio (T/C ratio); a value of < or =50% was indicative of gating. Auditory gating of the N2 wave was observed in the CA3, DG and mPFC. PCP disrupted gating in all three areas with significant increases in test amplitudes (P<0.001). Clozapine (5 mg/kg i.p) prevented the auditory gating deficits induced by PCP in the CA3, DG and mPFC. This study shows that PCP disrupts sensory gating in the CA3, DG and mPFC in the isoflurane anaesthetised rat. Similar deficits are observed in schizophrenic patients and the current method may provide an animal model with good predictive validity, a view substantiated by the fact that clozapine prevented the sensory gating deficits induced by PCP.
Dissanayake
Dilshani W N
DW
Department of Physiology, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 08, Sri Lanka.
Zachariou
Margarita
M
Marsden
Charles A
CA
Mason
Robert
R
D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001307:Auditory Perception / Q000502:physiology; D056654:CA3 Region, Hippocampal / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects*; D004567:Electrodes, Implanted; D004594:Electrophysiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D009433:Neural Inhibition / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D055139:Sensory Gating / Q000187:drug effects*; D012815:Signal Processing, Computer-Assisted
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D010622:Phencyclidine; D003024:Clozapine