Download PDF
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)

Also available at
    Permissions and Reprints

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

References

  • 1 Adachi N, Onuma T, Nishiwaki S, Murauchi S, Akanuma N, Ishida S, Takei N. Inter-ictal and post-ictal psychoses in frontal lobe epilepsy: a retrospective comparison with psychoses in temporal lobe epilepsy.  Seizure. 2000;  9 328-335
    CrossrefPubMedGoogle Scholar
  • 2 Akbarian S, Sucher N J, Bradley D. et al . Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics.  J Neurosci.. 1996;  16 19-30
    PubMedGoogle Scholar
  • 3 Allaoua H, Chicheportiche R. Anaesthetic properties of phencyclidine (PCP) and analogues may be related to their interaction with Na+ channels.  Eur J Pharmacol. 1989;  163 327-335
    CrossrefPubMedGoogle Scholar
  • 4 Arvanov V L, Liang X, Schwartz J, Grossman S, Wang R Y. Clozapine and haloperidol modulate N-methyl-D-aspartate- and non-N-methyl-D-aspartate receptor-mediated neurotransmission in rat prefrontal cortical neurons in vitro.  J Pharmacol Exp Ther. 1997;  283 226-234
    PubMedGoogle Scholar
  • 5 Avoli M, Louvel J, Pumain R, Olivier A. Seizure-like discharges induced by lowering [Mg2+]o in the human epileptogenic neocortex maintained in vitro.  Brain Res. 1987;  417 199-203
    CrossrefPubMedGoogle Scholar
  • 6 Briellmann R S, Kalnins R M, Hopwood M .J, Ward C, Berkovic S F, Jackson G D. TLE patients with postictal psychosis: mesial dysplasia and anterior hippocampal preservation.  Neurology. 2000;  55 1027-1030
    PubMedGoogle Scholar
  • 7 Coan E J, Collingridge G L. Effects of phencyclidine, SKF 10,047 and related psychotomimetic agents on N-methyl-D-aspartate receptor mediated synaptic responses in rat hippocampal slices.  Br J Pharmacol. 1987;  91 547-556
    CrossrefPubMedGoogle Scholar
  • 8 Contreras C M, Dorantes M E, Mexicano G, Guzman-Flores C. Lateralization of spike and wave complexes produced by hallucinogenic compounds in the cat.  Exp Neurol. 1986;  92 467-478
    CrossrefPubMedGoogle Scholar
  • 9 Cook C E, Brine D R, Jeffcoat A R, Hill J M, Wall M E, Perez-Reyes M, Di Guiseppi S R. Phencyclidine disposition after intravenous and oral doses.  Clin Pharmacol Ther. 1982;  31 625-634
    PubMedGoogle Scholar
  • 10 Cook C E, Brine D R, Quin G D, Perez-Reyes M, Di Guiseppi S R. Phencyclidine and phenylcyclohexene disposition after smoking phencyclidine.  Clin Pharmacol Ther.. 1982;  31 635-641
    PubMedGoogle Scholar
  • 11 Diehl L W. Schizophrenic syndromes in epilepsies.  Psychopathology. 1989;  22 65-140
    CrossrefPubMedGoogle Scholar
  • 12 Flor-Henry P. Psychosis and temporal lobe epilepsy.  Epilepsia. 1969;  10 363-395
    PubMedGoogle Scholar
  • 13 Friston K J, Frith C D. Schizophrenia: a disconnection syndrome?.  Clin Neurosci. 1995;  3 89-97
    PubMedGoogle Scholar
  • 14 Friston K J. The disconnection hypothesis.  Schizophr Res. 1998;  30 115-125
    CrossrefPubMedGoogle Scholar
  • 15 Gao W J, Krimer L S, Goldman-Rakic P S. Presynaptic regulation of recurrent excitation by D1 receptors in prefrontal circuits.  Proc Natl Acad Sci USA.. 2001;  98 295-300
    CrossrefPubMedGoogle Scholar
  • 16 Gonzalez-Pal S, Faure A, Quintana J, Fabelo R, Dominguez M E, Gomez-Plasencia R, Sanchez M J. Frontal lobe dysfunction in patients with epilepsy and chronic psychosis.  Rev Neurol. 1999;  28 219-223
    PubMedGoogle Scholar
  • 17 Gorji A, Khaleghi Ghadiri M. History of epilepsy in Medieval Iranian medicine.  Neurosci Biobehav Rev. 2001;  25 455-461
    CrossrefPubMedGoogle Scholar
  • 18 Gorji A, Scheld H H, Speckmann E -J. Epileptogenic effect of cyclosporine in guinea pig hippocampal slices.  Neuroscience. 2003;  115(4) 993-997
    PubMedGoogle Scholar
  • 19 Greene R. Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia.  Hippocampus. 2001;  11 569-577
    CrossrefPubMedGoogle Scholar
  • 20 Grunze H C, Rainnie D G, Hasselmo M E, Barkai E, Hearn E F, McCarley R W, Greene R W. NMDA-dependent modulation of CA1 local circuit inhibition.  J Neurosci. 1996;  16 2034-2043
    PubMedGoogle Scholar
  • 21 Hemmingsen R, Madsen A, Glenthoj B, Rubin P. Cortical brain dysfunction in early schizophrenia: secondary pathogenetic hierarchy of neuroplasticity, psychopathology and social impairment.  Acta Psychiatr Scand. 1999;  395 S80-88
    PubMedGoogle Scholar
  • 22 Hondo H, Yonezawa Y, Nakahara T, Nakamura K, Hirano M, Uchimura H, Tashiro N. Effect of phencyclidine on dopamine release in the rat prefrontal cortex; an in vivo microdialysis study.  Brain Res.. 1994;  633 337-342
    CrossrefPubMedGoogle Scholar
  • 23 Hwa G G, Avoli M, Oliver A, Villemure J G. Bicuculline-induced epileptogenesis in the human neocortex maintained in vitro.  Exp Brain Res. 1991;  83 329-339
    PubMedGoogle Scholar
  • 24 Jardemark K E, Liang X, Arvanov V, Wang R Y. Subchronic treatment with either clozapine, olanzapine or haloperidol produces a hyposensitive response of the rat cortical cells to N-methyl-D-aspartate.  Neuroscience. 2000;  100 1-9
    CrossrefPubMedGoogle Scholar
  • 25 Javitt D C, Zukin S R. Recent advances in the phencyclidine model of schizophrenia.  Am J Psychiatry. 1991;  148 1301-1308
    PubMedGoogle Scholar
  • 26 Jentsch J D, Taylor J R. Impaired inhibition of conditioned responses produced by subchronic administration of phencyclidine to rats.  Neuropsychopharmacology. 2001;  24 66-74
    CrossrefPubMedGoogle Scholar
  • 27 Jentsch J D, Tran A, Le D, Youngren K D, Roth R H. Subchronic phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal cortical-dependent cognition in the rat.  Neuropsychopharmacology. 1997;  17 92-99
    CrossrefPubMedGoogle Scholar
  • 28 Jentsch J D, Tran A, Taylor J R, Roth R H. Prefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence.  Psychopharmacology (Berl). 1998;  138 89-95
    CrossrefPubMedGoogle Scholar
  • 29 Koh D S, Geiger J R, Jonas P, Sakmann B. Ca(2+)-permeable AMPA and NMDA receptor channels in basket cells of rat hippocampal dentate gyrus.  J Physiol. 1995;  485 383-402
    PubMedGoogle Scholar
  • 30 Kumlien E, Hartvig P, Valind S, Oye I, Tedroff J, Langstrom B. NMDA-receptor activity visualized with (S)-[N-methyl-11C]ketamine and positron emission tomography in patients with medial temporal lobe epilepsy.  Epilepsia. 1999;  40 30-37
    PubMedGoogle Scholar
  • 31 Logsdail S J, Toone B K. Post-ictal psychoses. A clinical and phenomenological description.  Br J Psychiatry. 1988;  152 246-252
    CrossrefPubMedGoogle Scholar
  • 32 Matsuzaki M, Dowling K C. Phencyclidine (PCP): effects of acute and chronic administration on EEG activities in the rhesus monkey.  Electroencephalogr Clin Neurophysiol. 1985;  60 356-366
    PubMedGoogle Scholar
  • 33 Mountcastle V B. The columnar organization of the neocortex.  Brain. 1997;  120 701-722
    CrossrefPubMedGoogle Scholar
  • 34 Najm I M, Ying Z, Babb T ,. et al . Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.  Epilepsia. 2000;  41 971-976
    PubMedGoogle Scholar
  • 35 O’Shaughnessy C T, Lodge D. N-methyl-D-aspartate receptor-mediated increase in intracellular calcium is reduced by ketamine and phencyclidine.  Eur J Pharmacol. 1988;  153 201-209
    CrossrefPubMedGoogle Scholar
  • 36 Popoli P, Pezzola A, Benedetti M, Scotti de Carolis A. Verapamil and flunarizine inhibit phencyclidine-induced effects: an EEG and behavioural study in rats.  Neuropharmacology. 1992;  31 1185-1191
    CrossrefPubMedGoogle Scholar
  • 37 Proksch J W, Gentry W B, Owens S M. The effect of rate of drug administration on the extent and time course of phencyclidine distribution in rat brain, testis, and serum.  Drug Metab Dispos.. 2000;  28 742-747
    PubMedGoogle Scholar
  • 38 Rappolt RT S r, Gay G R, Farris R D. Phencyclidine (PCP) intoxication: diagnosis in stages and algorithms of treatment.  Clin Toxicol. 1980;  16 509-529
    PubMedGoogle Scholar
  • 39 Sachdev P. Schizophrenia-like psychosis and epilepsy: the status of the association.  Am J Psychiatry. 1998;  155 325-336
    PubMedGoogle Scholar
  • 40 Savard G, Andermann F, Olivier A, Remillard G M. Postictal psychosis after partial complex seizures: a multiple case study.  Epilepsia. 1991;  32 225-231
    PubMedGoogle Scholar
  • 41 Seeck M, Alberque C, Spinelli L, Michel C M, Jallon P. de Tribolet N, Landis T. Left temporal rhythmic electrical activity: a correlate for psychosis? A case report.  J Neural Transm. 1999;  106 787-794
    CrossrefPubMedGoogle Scholar
  • 42 Seeman P. Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4.  Neuropsychopharmacology. 1992;  7 261-284
    PubMedGoogle Scholar
  • 43 Selemon L D, Rajkowska G, Goldman-Rakic P S. Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17.  Arch Gen Psychiatry. 1995;  52 805-818
    PubMedGoogle Scholar
  • 44 So N K, Savard G, Andermann F, Olivier A, Quesney L F. Acute postictal psychosis: a stereo EEG study.  Epilepsia. 1990;  31 188-193
    PubMedGoogle Scholar
  • 45 Speckmann E J, Kohling R, Lucke A ,. et al . Microcutting of living brain slices by a pulsed ultrafine water jet which allows simultaneous electrophysiological recordings (micromingotome).  J Neurosci Methods. 1998;  82 53-58
    CrossrefPubMedGoogle Scholar
  • 46 Takeda Y, Inoue Y, Tottori T, Mihara T. Acute psychosis during intracranial EEG monitoring: close relationship between psychotic symptoms and discharges in amygdala.  Epilepsia. 2001;  42 719-724
    CrossrefPubMedGoogle Scholar
  • 47 Taylor D C. Factors influencing the occurrence of schizophrenia-like psychosis in patients with temporal lobe epilepsy.  Psychol Med. 1975;  5 249-254
    PubMedGoogle Scholar
  • 48 Telfeian A E, Connors B W. Epileptiform propagation patterns mediated by NMDA and non-NMDA receptors in rat neocortex.  Epilepsia. 1999;  40 1499-1506
    PubMedGoogle Scholar
  • 49 Vincent J P, Bidard J N, Lazdunski M, Romey G, Tourneur Y. Vignon J. Identification and properties of phencyclidine-binding sites in nervous tissues.  Fed Proc. 1983;  42 2570-2573
    PubMedGoogle Scholar
  • 50 Vollenweider F X. Advances and pathophysiological models of hallucinogenic drug actions in humans: a preamble to schizophrenia research.  Pharmacopsychiatry. 1998;  Suppl 2 92-103
    PubMedGoogle Scholar
  • 51 Wang X J. Synaptic basis of cortical persistent activity: the importance of NMDA receptors to working memory.  J Neurosci. 1999;  19 9587-9603
    PubMedGoogle Scholar
  • 52 Wong B Y, Prince D A. The lateral spread of ictal discharges in neocortical brain slices.  Epilepsy Res. 1990;  7 29-39
    CrossrefPubMedGoogle Scholar
  • 53 Wong R K, Miles R, Traub R D. Local circuit interactions in synchronization of cortical neurones.  J Exp Biol. 1984;  112 169-178
    PubMedGoogle Scholar

A. Gorji, M.D.

Institut für Physiologie

Universität Münster

Robert Koch-Strasse 27a

D-48149 Münster

Germany

Phone: +49-251-8355564

Fax: +49-251-8355551

Email: gorjial@uni-muenster.de

      >