Amygdala Hyperspindling and Seizures Induced by Cocaine

  • E. H. EllinwoodJr.
  • M. M. Kilbey
  • S. Castellani
  • C. Khoury
Part of the Advances in Behavioral Biology book series (ABBI, volume 21)


The temporal-lobe-like seizures produced by local anesthetics (deJong and Walts, 1966) have at least two possibly important contributions to human pathological conditions: 1) they may help explain the mechanisms underlying temporal lobe epilepsy and/or psychosis occasionally associated with this condition; 2) they may help elucidate the intervening links between the association of the overactivity of the limbic spindle and limbic discharges, with hyperarousal and hyperactive behaviors noted in animal models of chronic stimulant psychosis (see Ellinwood, 1974a for review). Chronic high-dose amphetamine (25–35 mg/kg) administration, or self-administration, in the cat results in bizarre hyperreactive behavior and associated high voltage limbic spindles that may precede tonic-clonic seizures. Furthermore, in chronic high dose amphetamine-intoxicated animals, specific hyperreactive behaviors (at times the animal appears to be reacting to non-existent stimuli) are often immediately preceded by a high voltage spindle and/or discharge in the amygdala, accumbens, and olfactory tubercle (Ellinwood, 1974a; Ellinwood, Sudilovsky, and Nelson, 1974). Much lower doses of amphetamine (10 mg/kg) when administered concomitantly with disulfiram (a dopamine beta hydroxylase inhibitor blocking norepinephrine [NE] synthesis) for only two to three days produces bizarre hyperreactive behavior with hyperspindling leading to tonicclonic seizures (Ellinwood, Sudilovsky, and Grabowy, 1973).


Olfactory Bulb Temporal Lobe Epilepsy Olfactory Tubercle Cocaine Injection Behavioral Seizure 
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  1. Appelbaum, M.I.: The MANOVA Manual; Complete Factorial Design (Research Memorandum Number 44 of the L.L. Thurstone Psychometric Laboratory). Chapel Hill, N.C.: The L.L. Thurstone Psychometric Laboratory of the University of North Carolina, 1974.Google Scholar
  2. Arnold, P.S., Racine, R.J., and Wise, R.A.: Effects of atropine, reserpine, 6-hydroxydopamine, and handling on seizure development in the rat, Expl Neurol. 40, 457–470 (1973).CrossRefGoogle Scholar
  3. Balster, R.L., Kilbey, M.M., and Ellinwood, E.H.: Methamphetamine self-administration in the cat, Psychopharmacologia 46, 229–233 (1976).PubMedCrossRefGoogle Scholar
  4. Barlow, J.S. and Freeman, M.Z.: Comparison of EEG activity recorded from analogous locations on the scalp by means of autocorrelation and cross-correlation analysis, Quarterly Progress Report (M.I.T. Research Laboratory of Electronics) 54, 173–181 (1959).Google Scholar
  5. Bell, D.S.: The experimental reproduction of amphetamine psychosis,Archs gen. Psychiat. 29, 35–40 (1973).CrossRefGoogle Scholar
  6. Bernhard, C.G. and Bohm, E.: The action of local anesthetics on experimental epilepsy in cats and monkeys, Br. J. Pharmacol. 10, 288–295 (1955).Google Scholar
  7. Bernhard, C.G. and Bohm, E.: Local Anesthetics and Anticonvulsants: A Study on Experimental and Clinical Epilepsy. Stockholm: Almgvist and Wiksell, 1965.Google Scholar
  8. Brazier, M.A.B.: Interactions of deep structures during seizures in man. In: Synchronization of EEG Activity in Epilepsia. Petsche, H. and Brazier, M.A.B., Eds., pp. 409–424. Vienna: Springer-Verlag, 1972.CrossRefGoogle Scholar
  9. Corcoran, M.E., Fibiger, H.C., McCaughran, J.A., and Wada, J.A.: Potentiation of amygdaloid kindling and metrazol-induced seizures by 6-hydroxydopamine in rats, Expl Neurol. 45, 118–133 (1974).CrossRefGoogle Scholar
  10. Eidelberg, E., Lesse, H., and Gault, F.P. An experimental model of temporal lobe epilepsy: Studies on the convulsant properties of cocaine. In: EEG and Behavior. Gilbert, H. and Glaser, G.H., Fds., pp. 272–283. New York: Basic Books, 1963.Google Scholar
  11. Eidelberg, E., Neer, H.M., and Miller, M.K.: Anticonvulsant properties of some benzodiazepine derivatives, Neurology, Minneap. 15, 223 (1965).PubMedCrossRefGoogle Scholar
  12. Ellinwood, E.H.: Effect of chronic methamphetamine intoxication in rhesus monkeys, Biol. Psychiat. 3, 25–2 (1971).PubMedGoogle Scholar
  13. Ellinwood, E.H.: Amphetamine and stimulant drugs. In: Drug Use in America: Problem in Perspective (Second Report of the National Commission on Marihuana and Drug Abuse), pp. 140–157. Washington: U.S. Government Printing Office, 1973.Google Scholar
  14. Ellinwood, E.H., Sudilovsky, A., and Grabowy, R.S.: Olfactory forebrain seizures induced by methamphetawine and disulfiram, Biol. Psychiat. 7, 89–99 (1973).PubMedGoogle Scholar
  15. Ellinwood, E.H.: Behavioral and EEG changes in the amphetamine model of psychosis. In: Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes. Usdin, E., Ed., pp. 281–297. New York: Raven Press, 1974a.Google Scholar
  16. Ellinwood, E.H.: Physiological aspects of cocaine. Paper presented at NIDA conference on cocaine research, Washington, D.C., 1974b.Google Scholar
  17. Ellinwood, E.H., Sudilovsky, A., and Nelson, L.: Behavior and EEG analysis of chronic amphetamine effect, Biol. Psychiat. 8, 169–176 (1974).PubMedGoogle Scholar
  18. Ellinwood, E.H. and Kilbey, M.M.: Amphetamine stereotypy: The influence of environmental factors and prepotent behavioral patterns on its topography and development, Biol. Psychiat. 10, 3–16 (1975).PubMedGoogle Scholar
  19. Escalante, O.D. and Ellinwood, E.H.: Central nervous system cytopathological changes in cat with chronic methedrine intoxication, Brain Res. 21, 151–155 (1970).PubMedCrossRefGoogle Scholar
  20. Fish, F.J.: A neurophysiological theory of schizophrenia, J. ment. Sci. 107, 828 (1961).PubMedGoogle Scholar
  21. Flor-Henry, P.: Psychosis and temporal lobe epilepsy: A controlled investigation, Epilepsia 10, 363–395 (1968).CrossRefGoogle Scholar
  22. French, J.D., Livingston, R.V., Konigsmark, B., and Richland, K.J.: Experimental observations on the prevention of seizures by intravenous procaine injections, J. Neurosurgery 14, 43–54 (1957).CrossRefGoogle Scholar
  23. Goddard, G.V.: Development of epileptic seizures through brain stimulation at low intensity, Nature, Lond. 214, 1020–1021 (1967).CrossRefGoogle Scholar
  24. Grabowy, R.S. and Ellinwood, E.H.: On-line detection of EEG spindle activity, Decus Spring Symposiums 42–45 (1971).Google Scholar
  25. deJong, R.H. and Walts, L.F.: Lidocaine induced psychomotor seizures in man, Acta Anaesth. scand., Suppl. 23, 598–604 (1966).Google Scholar
  26. deJong, R.H.: Local anesthetic seizures, Anesthesiology 30, 5–6 (1969).Google Scholar
  27. deJong, R.H.: Physiology and Pharmacology of Local Anesthesia. Springfield, Ill.: Charles C. Thomas, 1970.Google Scholar
  28. Kramer, J.C.: Introduction to amphetamine abuse, J. Psychedelic Drugs 2, 1–16 (1969).Google Scholar
  29. Matousek, M.: Frequency and correlation analysis. of Electroencephalography and Clinical Neuroph Remond, A., Ed., Vol. 5, Part A. Amsterdam: tific Publishing Company, 1973.Google Scholar
  30. McCall, R.B. and Appelbaum, M.I.: Bias in the analysis of repeated-measure designs: Some alternative approaches, Child Dev. 44, 401–415 (1973).CrossRefGoogle Scholar
  31. Modigh, K.: Electroconvulsant shock in post-synaptic catecholamine effects: Increased psychomotor stimulant action of apomorphine and clonidine in reserpine pretreated mice by ECT, J. Neural Transm. 36, 19–32 (1975).PubMedCrossRefGoogle Scholar
  32. De Oliveira, L.F. and Bretas, A.D.: Effects of 5-hydroxytryptophan, ipromazid and p-chlorophenylalanine on lidocaine seizure threshold of mice, Eur. J. Pharmacol. 29, 5–9 (1974).PubMedCrossRefGoogle Scholar
  33. Pinel, J.P.J., Phillips, A.G., and MacNeil, B.: Blockage of highly- stable “kindled” seizures in rats by antecedent footshock, Epilepsia 14, 29–37 (1973).PubMedCrossRefGoogle Scholar
  34. Post, R.M.: Progressive changes in behavior and seizures following chronic cocaine administration: Relationship to kindling and psychosis. In: Cocaine and Other Stimulants. Ellinwood, E.H. and Kilbey, M.M., Eds. New York: Plenum Press, 1976.Google Scholar
  35. Riblett, L.A. and Tuttle, W.W.: Investigation of the amygdaloid and olfactory electrographic response in the cat after toxic dosages of lidocaine, Electroenceph .clin. Neurophysiol. 38, 601–608Google Scholar
  36. Rumbaugh, C.L.: Small vessel cerebral vascular changes following chronic amphetamine intoxication. In: Cocaine and Other Stimulants. Ellinwood, E.H. and Kilbey, M.M., Eds. New York: Plenum Press, 1976.Google Scholar
  37. Sanders, H.D.: Procaine and pentylenetetrazol, Archs int. Pharmacodyn. TILL.. 170, 115–177 (1967).Google Scholar
  38. Seiden, L.S., Fischman, M.W., and Schuster, C.R.: Changes in brain catecholamines induced by long-term methamphetamine administration in rhesus monkeys. In: Cocaine and Other Stimulants. Ellinwood, E.H. and Kilbey, M.M., Eds. New York: Plenum Press, 1976.Google Scholar
  39. Stripling, J.S. and Ellinwood, E.H.: Sensitization to cocaine following chronic administration in rats. In: Cocaine and Other Stimulants. Ellinwood, E.H. and Kilbey, M.M., Eds. New York: Plenum Press, 1976.Google Scholar
  40. Tuttle, W.W. and Elliott, H.W.: Electrographic and behavioral study of convulsants in the cat, Anesthesiology 30, 48–64 (1969)PubMedCrossRefGoogle Scholar
  41. Utena, H.: On relapse-liability, schizophrenia, amphetamine psychosis and animal model. In: Biological Mechanisms of Schizophrenia and Schizophrenia-like Psychoses. Mitsuda, H. and Fukuda, T., Eds., p. 285. Tokyo: igaku Shoin, 1974.Google Scholar
  42. Wada, J.A. and Sata, M.: Generalized convulsive seizures induced by daily electrical stimulation of the amygdala in cats: Correlative electrographic and behavioral features, Neurology, Minneap. 24, 565–574 (1974).PubMedCrossRefGoogle Scholar
  43. Wagman, I.H., deJong, R.H., and Prince, D.A.: Effect of lidocaine on central nervous system, Anesthesiology 28, 155–172 (1967).PubMedCrossRefGoogle Scholar
  44. Wagman, I.H., deJong, R.H., and Prince, D.A.: Effects of lidocaine on spontaneous cortical and subcortical electrical activity: Production of seizure discharges, Archs Neurol., Chicago 18, 277 (1968).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • E. H. EllinwoodJr.
    • 1
  • M. M. Kilbey
    • 1
  • S. Castellani
    • 1
  • C. Khoury
    • 1
  1. 1.Behavioral Neuropharmacology Section, Department of PsychiatryDuke University Medical CenterDurhamUSA

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