Progressive Changes in Behavior and Seizures Following Chronic Cocaine Administration: Relationship to Kindling and Psychosis

  • Robert M. Post
Part of the Advances in Behavioral Biology book series (ABBI, volume 21)


In this paper we will focus on the effects of repetitive cocaine administration on a variety of neurological, behavioral, and biochemical parameters. We will pay selective attention to the data suggesting that repetitive administration may be associated with increased effects on a variety of parameters, and will not review data suggesting that cocaine may produce tolerance in some systems. While we will present our findings of the effects of repetitive cocaine administration in laboratory animals, particularly the rat and rhesus monkey, they also appear relevant to the effects of stimulants in man. It has been reviewed in detail elsewhere that chronic administration of amphetamine-like stimulants may produce a paranoid psychosis difficult to distinguish from paranoid schizophrenia (Ellinwood, 1972; Connell, 1958; Snyder, 1973; Angrist, Gershon, 1970; Griffith, Cavanaugh, Held, Oates, 1970; Änggard, Jonsson, Hogmark, Gunne, 1973). Initial or lower doses of stimulants in a variety of patient populations, on the contrary, appear to elicit predominantly affective responses in the euphoric-dysphoric spectrum (Post, Kotin, Goodwin, 1974; Post, 1975; Resnick, Schwartz, Kestenbaum, Freedman, 1975). An adequate exposition of the mechanisms involved in the transition from predominantly affective symptoms to those in the schizophreniform spectrum with chronic stimulant administration, has not been adequately given.


Rhesus Monkey Cocaine Administration Paranoid Schizophrenia Chronic Cocaine Psychomotor Stimulant 
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  1. Änggard, E., Jonsson, L.E., Hogmark, A.L. and Gunne, L.M.: Amphetamine metabolism in amphetamine psychosis, Clin. Pharmacol. Therap. 14, 870–880 (1973).Google Scholar
  2. Angrist, B. and Gershon, S.: The phenomenology of experientially induced amphetamine psychosis: Preliminary observations, Biol. Psychiat. 2, 95–107 (1970).PubMedGoogle Scholar
  3. Arieti, S.: Interpretation of Schizophrenia. Pp. 423–433. New York: Basic Books, 1974.Google Scholar
  4. Connell,. P.H.: Amphetamine Psychosis. New York: Oxford University Press, 1958.Google Scholar
  5. Cools, A.R., Hendriks, G., and Korten, J.: The acetylcholine-dopamine balance in the basal ganglia of rhesus monkeys and its role in dynamic, dystonic, dyskinetic, and epileptoid motor activities, J. Neural Trans. 36, 91 (1975).CrossRefGoogle Scholar
  6. Costall, B. and Naylor, R.: Neuroleptic antagonism of dyskinetic phenomena, Eur. J. Pharmacol. 33, 301–312 (1975).PubMedCrossRefGoogle Scholar
  7. Creese, I., Burt, D.R., and Snyder, S.H.: Dopamine receptor binding: Differentiation of agonist and antagonist states with 3H-dopamine and 3H-Haloperidol, Life Sci. 17, 993–1002 (1975).CrossRefGoogle Scholar
  8. Downs, A.W. and Eddy, N.B.: The effect of repeated doses of cocaine on the rat, J. Pharmac. exp. Ther. 46, 199–200 (1932).Google Scholar
  9. Eidelberg, E., Lesse, H., and Gault, F.P.: Experimental model of temporal lobe epilepsy: Studies of convulsant properties of cocaine. In: EEG and Behavior. Glaser, G.H., Ed., pp. 272–283. New York: Basic Books, 1963.Google Scholar
  10. Ellinwood, E.H.: Amphetamine psychosis: Individuals, settings, and sequences. In: Current Concepts on Amphetamine Abuse. Ellinwood, E.H. and Cohen, S., Eds., pp. 143–157. Washington: U.S. Government Printing Office, 1972.Google Scholar
  11. Ellinwood, E.H. and Escalante, O.: Chronic amphetamine effect on the olfactory forebrain, Biol. Psychiat. 2, 189–203 (1970).PubMedGoogle Scholar
  12. Ellinwood, E.H. and Kilbey, M.M. Amphetamine stereotypy: The factors and prepotent behavioral and development, influence of environmental patterns on its topography Biol. Psychiat. 10, 3–16 (1975)PubMedGoogle Scholar
  13. Ellinwood, E.H., Sudilovsky, A., and Nelson, L.: Behavioral analysis of amphetamine intoxication, Biol. Psychiat. 3, 215–230 (1972).Google Scholar
  14. Escalante, O.D. and Ellinwood, E.H.: CNS cytopathological changes in cats with chronic methedrine intoxication, Brain Res. 21, 151–155 (1970).PubMedCrossRefGoogle Scholar
  15. Feinberg, G. and Irwin, S.: Effects of chronic methamphetamine administration in the cat, Fed. Proc. 20, 396 (1961).Google Scholar
  16. Goddard, G.V., McIntyre, D.C., and Leech, C.K.: A permanent change in brain function resulting from daily electrical stimulation, Exp. Neurol. 25, 295–330 (1969).PubMedCrossRefGoogle Scholar
  17. Griffith, J.D., Cavanaugh, J.H., Held, J., and Oates, J.A.: Experimental psychosis induced by the administration of d-amphetamine. In: Amphetamines and Related Compounds. Costa, E. and Garattini, S., Eds., pp. 897–904. New York: Raven Press, 1970.Google Scholar
  18. Groves, P.M., Wilson, C.J., Young, S.T., and Rebec, G.V.: Self-inhibition of dopaminergic neurons, Science 190, 522–529 (1975).PubMedCrossRefGoogle Scholar
  19. Gutierrez-Noriega, C.: Inhibition of central nervous systems produced by chronic cocaine intoxication, Fed. Proc. 9, 280 (1950).Google Scholar
  20. Klawans, H.L. and Margolin, D.I.: Amphetamine-induced dopaminergic sensitivity in guinea pigs, Arch. gen. Psychiat. 32, 725–732 (1975) .PubMedCrossRefGoogle Scholar
  21. Kluver, H. and Bucy, P.C.: Psychic blindness and other symptoms following bilateral temporal lobectomy in rhesus monkeys, Am. J. Physiol. 119, 352–353 (1937).Google Scholar
  22. Kramer, J.C.: Introduction to amphetamine abuse. In: Current Concepts on Amphetamine Abuse. Ellinwood, E.H. and Cohen, S., Eds., pp. 177–184. Washington: U.S. Government Printing Office, 1972.Google Scholar
  23. Leech, C.K.: Sound-induced kindling resulting from daily bursts of loud noise presented to seven strains of mouse. Paper presented at Canadian Psychological Association Meeting, St. John’s, Newfoundland, June 3, 1971.Google Scholar
  24. Lesse, H., Heath, R.G., Mickle, W.A., Munroe, R.R., and Miller, W.H.: Rhinencephalic activity during thought, J. nerv. ment. Dis. 122, 433–440 (1955).PubMedCrossRefGoogle Scholar
  25. Libet, B. and Tosaka, T.: Dopamine as a synaptic transmitter and modulator in sympathetic ganglia: A different mode of synaptic action, Proc. natn. Acad. Sci. U.S.A. 67, 667–673 (1970).CrossRefGoogle Scholar
  26. Mason, C.R. and Cooper, R.M.: A permanent change in convulsive threshold in normal and brain damaged rats with small repeated doses of pentylenetetrazol, Epilepsia 13, 663–674 (1972).PubMedCrossRefGoogle Scholar
  27. Modigh, K.: Electroconvulsant shock and postsynaptic catecholamine effects: Increased psychomotor stimulant action of apomorphine and clonidine in reserpine pretreated mice by repeated FCS, J. Neural Trans. 36, 19–32 (1975).CrossRefGoogle Scholar
  28. Nayak, P.K., Misra, A.L., and Mulé, S.: Physiological disposition and biotransformation of (3H) cocaine in acutely-and chronically-treated rats, J. Pharmac. exp. Ther. 196, 556–569 (1976).Google Scholar
  29. Pinel, J.P.J. and Van Oot, P.H.: Generality of the kindling phenomenon: Some clinical implications, Can. J. Neurosci., in press.Google Scholar
  30. Post, R.M.: Cocaine psychoses: A continuum model, Am. J. Psychiat. 132, 225–231 (1975).PubMedGoogle Scholar
  31. Post, R.M. and Kopanda, R.T.: Cocaine, kindling, and reverse tolerance, Lancet 1, 409–410 (1975).PubMedCrossRefGoogle Scholar
  32. Post, R.M. and Kopanda, R.T.: Cocaine, kindling, and psychosis, Am. J. Psychiat., in press.Google Scholar
  33. Post, R.M., Kotin, J., and Goodwin, F.K.: The effects of cocaine on depressed patients, Am. J. Psychiat. 131, 511–517 (1974).PubMedGoogle Scholar
  34. Post, R.M., Kopanda, R.T., and Lee, A.: Progressive development of coprophagia and seizures during chronic lidocaine administration: Relationship to kindling and psychosis, Life Sci. 17, 943–950 (1975).PubMedCrossRefGoogle Scholar
  35. Post, R.M., Kopanda, R.T., and Black, K.E.: Progressive effects of cocaine on behavior and central amine metabolism in rhesus monkeys, Biol. Psychiat., in press.Google Scholar
  36. Prichard, J.W., Gallagher, B.B., and Glaser, G.H.: Experimental seizure-threshold testing with flurothyl, J. Pharmac. exp. Ther. 166, 170–178 (1969).Google Scholar
  37. Racine, R.J.: Modification of seizure activity by electrical stimulation. II. Motor seizure, Electroenceph. clin. Neurophysiol. 32, 281–294 (1972).PubMedCrossRefGoogle Scholar
  38. Ranje, C. and Ungerstedt, U.: Chronic amphetamine treatment: Vast individual differences in performing a learned response, Eur. J. Pharmacol. 29, 307–311 (1974).PubMedCrossRefGoogle Scholar
  39. Resnick, R.B., Schwartz, L.K., Kestenbaum, R.S., and Freedman, A.M.: Cocaine dose-response curves in man. Paper presented at the Annual Meeting of the Society of Biological Psychiatry, New York, 1975.Google Scholar
  40. Riblet, L.A. and Tuttle, W.W.: Investigation of the amygdaloid and olfactory electrographic response in the cat after toxic dosage of lidocaine, Electroenceph. clin. Neurophysiol. 28, 601–608 (1970).PubMedCrossRefGoogle Scholar
  41. Roth, P.H., Walters, J.R., Murrin, L.C., and Morgenroth, V.H.: Dopamine neurons: Role of impulse flow and presynaptic receptors in the regulation of tyrosine hydroxylase. In: Pre-and Post-Synaptic Receptors. Usdin, E., and Bunney, W.E., Eds., pp. 5–48. New York: Marcel Dekker, 1975.Google Scholar
  42. Segal, D.S. and Mandell, A.J.: Long-term administration of d-amphetamine: Progressive augmentation of motor activity and stereotypy, Pharmac. Biochem. Behay. 2, 249–255 (1974).CrossRefGoogle Scholar
  43. Snyder, S.H.: Amphetamine psychosis: A “model” schizophrenia mediated by catecholamines, Am. J. Psychiat. 130, 61–67 (1973).PubMedGoogle Scholar
  44. Tatum, A.L. and Seevers, M.H.: Experimental cocaine addiction, J. Pharmac. exp. Ther. 36, 401–410 (1929).Google Scholar
  45. Tilson, H.A. and Rech, R.H.: Conditioned drug effects and absence of tolerance to d-amphetamine-induced motor activity, Pharmac. Biochem. Behay. 1, 149–153 (1973).CrossRefGoogle Scholar
  46. Vosu, H. and Wise, R.A.: Cholinergic seizure kindling in the rat: Comparison of caudate, amygdala, and hippocampal, Behay. Biol. 13, 491–495 (1975).CrossRefGoogle Scholar
  47. Wada, J.A. and Sata, M.S.: Generalized convulsive seizures induced by daily electrical stimulation of the amygdala in cats, Neurology, Minneap. 24, 565–574 (1974).PubMedCrossRefGoogle Scholar
  48. Wagman, I.H., DeJong, R.H., and Prince, D.A.: Effects of lidocaine on spontaneous cortical and subcortical electrical activity, Arch. Neurol. 18, 277–290 (1968).PubMedCrossRefGoogle Scholar
  49. Zapata-Ortiz, V.: Modificaciones psicológicas y fisiológicas producidas par la coca y la cocaina en los coqueros, Revta. Med. exp. 3, 132–161 (1944).Google Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Robert M. Post
    • 1
  1. 1.Section on Psychobiology, Adult Psychiatry BranchNational Institute of Mental HealthBethesdaUSA

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