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Pharmacopsychiatry 2003; 36(3): 113-120
DOI: 10.1055/s-2003-39986
Original Paper
© Georg Thieme Verlag Stuttgart · New York

The Lateral Spread of Epileptiform Discharges in Rat Neocortical Slices: Effect of Focal Phencyclidine Application

A. Gorji1 , D. Scheller2 , E-J. Speckmann1, 3
  • 1Institut für Physiologie, Universität Münster, 48149 Münster, Germany
  • 2Janssen-Research Foundation, 41470 Neuss, Germany
  • 3Institut für Experimentelle Epilepsieforschung, Universität Münster, 48149 Münster, Germany
Further Information

Publication History

Received: 17.6.2002 Revised: 22.7.2002

Accepted: 11.9.2002

Publication Date:
13 June 2003 (online)

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In vitro and in vivo brain slice techniques were used to examine phencyclidine (PCP) effects on the lateral propagation of epileptiform field potentials (EFP) across adjacent areas of rat frontal neocortex. Epileptiform activity was induced by perfusing slices with Mg2+-free artificial cerebrospinal fluid. Simultaneous field potential recordings of EFP were obtained from four microelectrodes placed 2-3 mm apart across coronal slices in the third layer. PCP, applied focally between recording sites, blocked rapid propagation across treated areas and resulted in the emergence of spatially separate, independent pacemakers. The characteristics of paroxysmal depolarization shifts did not change significantly by the blockade of lateral propagation of EFP. The same asynchronized pattern of EFP conduction was observed after local application of the N-methyl-D-aspartate (NMDA)-receptor antagonist DL-2-amino-5-phosphono-valeric acid. Local administration of haloperidol as well as NMDA before PCP application reversibly prevented appearance of multiple pacemakers. Focal application of dopamine produced an abnormal pattern of lateral conduction of EFP in 50 % of tested slices. Pacemaker failure as an indicator of functional impairment of cortical integration is the proposed mechanism for developing of schizophrenia-like psychosis associated with epilepsy.

Abbreviations

APV:DL-2-amino-5-phosphono-valeric acid

EEG:electroencephalogram

EFP:epileptiform field potentials

NMDA:N-methyl-D-aspartate

PCP:phencyclidine

SLPE:Schizophrenialike psychosis associated with epilepsy

Key words

Seizure - cortex - inhibitory circuits - behavioral excitation - delusion

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A. Gorji, M.D.

Institut für Physiologie

Universität Münster

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D-48149 Münster

Germany

Phone: +49-251-8355564

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Email: gorjial@uni-muenster.de