Research Report Effects of phencyclidine on auditory gating in the rat hippocampus and the medial prefrontal cortex Dilshani W.N. Dissanayake a, ⁎ , Margarita Zachariou b , Charles A. Marsden c , Robert Mason c a Department of Physiology, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 08, Sri Lanka b School of Mathematical Sciences, University of Nottingham, NG7 2RD, UK c School of Biomedical Sciences, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK ARTICLE INFO ABSTRACT Article history: Accepted 7 August 2009 Available online 20 August 2009 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 ≤ 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. © 2009 Elsevier B.V. All rights reserved. Keywords: Sensory gating CA3 Dentate gyrus Medial prefrontal cortex Phencyclidine Clozapine 1. Introduction Sensory gating, a process in which the response of the brain to a repetitive stimulus is attenuated, is considered to contribute to information processing by enabling organisms to filter extrane- ous sensory inputs from the environment (Boutros et al., 1997; Joy et al., 2004; Cromwell et al., 2008). Sensory gating can be demonstrated in human subjects using auditory-evoked EEG responses (AERs) to a conditioning–testing paradigm, in which two identical auditory tones are presented 500 ms apart. Normal subjects have a smaller response to the second (test) tone compared to the first (conditioning) tone and the ratio of the BRAIN RESEARCH 1298 (2009) 153 – 160 ⁎ Corresponding author. Fax: +94 112691581. E-mail address: dilshani2003@yahoo.co.uk (D.W.N. Dissanayake). Abbreviations: DG, Dentate gyrus; PFC, Prefrontal cortex; mPFC, medial prefrontal cortex; AER, Auditory-evoked response; PCP, phencyclidine; CAMP, conditioning amplitude; TAMP, test amplitude 0006-8993/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2009.08.032 available at www.sciencedirect.com www.elsevier.com/locate/brainres