Skip to main content

Animal Models of Hallucinations

Continuous Stimulants

  • Protocol
Animal Models in Psychiatry, I

Part of the book series: Neuromethods ((NM,volume 18))

Abstract

When amphetamine or cocaine is administered to humans every hour or so for several days, either during the “speed runs” of addicts or in controlled laboratory settings, there reliably results a psychosis that is similar to paranoid schizophrenia in a number of important aspects. This unique regimen of amphetamine intake, involving the continuous presence of stimulants over a prolonged period of time, can be simulated in animals using subcutaneously implanted slow-release silicone pellets containing d-amphetamine or cocaine base. Monkeys and rats implanted with amphetamine pellets develop stages of behavioral alterations that are somewhat similar in sequence to those observed in humans who self-administer frequent doses of amphetamine. An initial period of hyperactivity and exploratory behavior is followed by the gradual development of motor stereotypies, then a period of relative inactivity, and finally, at three to five days after pellet implantation, by a late-stage. This final stage is characterized by “wet-dog” shakes, parasitotic-like grooming episodes, and a variety of other forms of hallucinatory like behavior.Because continuous amphetamine administration also induces distinctive, neurotoxic alterations in dopaminergic innervations of the caudate nucleus, but not in mesolibic dopamine innervation of the nucleus accumbens or in several other neurotransmitte systems, we initially hypothesized that the hallucinatory behaviors were a reflection, in part, of the damaged caudate dopamine terminals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • American Psychiatric Association. DSM-III: Diagnostic and Statistical Manual of Mental Disorders. 3rd Ed. Washington, DC: The Association, 1980.

    Google Scholar 

  • Angrist M. and Gershon S. (1970) The phenomenology of experimentally induced amphetamine psychosis— preliminary observations. Bio. Psychiat. 2, 95–107.

    CAS  Google Scholar 

  • Angrist B, Lee H. K., and Gershon S. (1974a) The Antagonism of amphetamine-induced symptomatology by aneuroleptic. Am. J. Psychiat. 131, 817–819.

    PubMed  CAS  Google Scholar 

  • Angrist B., Sathananthan G., Wilk S., and Gershon S. (1974b) Amphetamine psychosis: Behavioral and biochemical aspects. J. Psychiatu. Res. 11, 13–23.

    Article  CAS  Google Scholar 

  • Bell D. S. (1965) Comparison of amphetamine psychosis and schizophrenia. Am. Psychiat. 111, 701–707.

    CAS  Google Scholar 

  • Bell D. S. (1973) The experimental reproduction of amphetamine psychosis. Arch. Gen. Psychiat. 29, 35–40.

    PubMed  CAS  Google Scholar 

  • Bowers M. (1968) Pathogenesis of acute schizophrenic psychosis. Arch. Gen. Pychiatr. 19, 348–355.

    Google Scholar 

  • Connell P. (1958) Amyhetamine Psychosis, Maudsley Monographs No. 5. Oxford University Press, London.

    Google Scholar 

  • Eison M. S., Ellison G, and Eison A. S. (1981) The regional distribution of amphetamine in rat brain is altered by dosage and prior exposue to the drug. J. Pharmacol. Exy. Ther. 218, 237–241.

    CAS  Google Scholar 

  • Ellinwood E. H. (1981) Assault and homicide associated with amphetamine abuse. Am. J. Psychiat. 127, 1170–1175.

    Google Scholar 

  • Ellinwood E. H. and Kilbey M. (1977) Chronic stimulant intoxication models of psychosis, in Animal Models in Psychiatry and Neurology (Hanin I. and Udin E., eds.), Pergamon Press, New York, NY, pp. 61–74.

    Google Scholar 

  • Ellinwood E. H. and Sludilovsky A. (1973) Chronic amphetamine intoxication: Behavioral model of psychoses, in Psychoyuthology and Psychopharmacology (Cole J. O., Freedman A. M., and Friedhoff A. J., eds.), Johns Hopkins University Press, Baltimore, MD, p. 51–71.

    Google Scholar 

  • Ellinwood E. H. Jr. (1967) Amphetamine psychosis: I. Description of the individuals and the process. J. Nerv. Ment. Dis 144, 273–283.

    Article  Google Scholar 

  • Ellison G. and Morris W. (1981) Opposed stages of continuous amphetamine administration: Parallel alterations in motor sterotypies and in vivo spiroperidol accumulation. Eur J. Pharmacol. 74, 207–214.

    Article  PubMed  CAS  Google Scholar 

  • Ellison G. and Ratan R. (1982) The late-stage following continuous amphetamine administration to rats is correlated with altered dopamine but not serotonin metabolism. Life Sci. 31, 771–777.

    Article  PubMed  CAS  Google Scholar 

  • Ellison G, Eison M, Huberman H, and Daniel F. (1978) Structural and biochemical alterations in dopaminergic innervation of the caudate nucleus following continuous amphetamine administration. Science 201, 276–278.

    Article  PubMed  CAS  Google Scholar 

  • Ellison G, See R, Levin E., and Kinney J. (1987) Tremorous mouth movements in rats administered chronic neuroleptics. Psychophurmacol. 92, 122–126.

    Article  CAS  Google Scholar 

  • Ellison G., Staugaitis S., and Crane P. A. (1981b) A silicone delivery system for producing binge and continuous intoxication in rats. Pharmacol. Biochem. Behav. 14, 207–211.

    Article  PubMed  CAS  Google Scholar 

  • Ellison G, D., Nielsen E. B., and Lyon M. (1981) Animal models of psychosis: Hallucinatory behaviors in monkeys during the late-stage of continuous amphetamine intoxication. J. Psychiatr. Res. 16, 13–22.

    Article  PubMed  CAS  Google Scholar 

  • Ellison G. D. and Eison M. S. (1983) Continuous amphetamine intoxication: An animal model of the acute psychotic episode. Psychol. Med. 13, 751–761.

    Article  PubMed  CAS  Google Scholar 

  • Erickson C. K, Stavchanaky S. A., Koch K. I., and McGinity J. W. (1982) A new subcutaneously-implantable reservoir for sustained release of nicotine in the rat. Pharmacol. Biochem. Behav. 17, 183–185.

    Article  PubMed  CAS  Google Scholar 

  • Fuller R. and Hemrick-Luecke S. (1980) Long-lasting depletion of striatal dopamine by a single injection of amphetamine in iprindole-treated rats. Science 209, 305,306.

    Article  Google Scholar 

  • Gately P. F., Segal D. S., and Geyer M. A. (1987) Sequential changes in behavior induced by continuous infusions of amphetamine in rats. Psychopharmacology 91, 217–220.

    Article  PubMed  CAS  Google Scholar 

  • Gawin F. H. (1986) Neuroleptic reduction of cocaine-induced paranoia but not euphoria? Psychoyhumacofogy 90, 142,143.

    CAS  Google Scholar 

  • Gold M. S. and Bowers M. Jr. (1978) Neurobiological vulnerability to lowdose amphetamine psychosis. Am. J. Psychiat. 35, 1546–1548.

    Google Scholar 

  • Griffith J., Cavanaugh J., Held N., and Oates J. (1972) d-amphetamine: Evaluation of psychotomimetic propertiesinman. Arch. Gen. Pcsychiat. 26, 97–100.

    CAS  Google Scholar 

  • Hanson G. R, Matsuda L, and Gibb J. W. (1987) Effects of cocaine on methamphetamine-induced neurochemical changes: Characterization of cocaine as a monoamine uptake blocker. J. Phurmacol. Exp. Ther. 242, 507–513.

    CAS  Google Scholar 

  • Ho B. T., Taylor D. T., Estevez V. S., Englert L. F., and McKenna M. L. (1977) Behavioral effects of cocaine: Metabolic and neurochemical approach, in Cocaine and Other Stimulunts (Ellinwood E. H. and Kilbey M. M., eds.), Plenum, New York, pp. 229–240.

    Google Scholar 

  • Hotchkiss A. and Gibb J. (1980) Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. J. Pharmacol, Exp. Ther. 214, 257–262.

    CAS  Google Scholar 

  • Huberman H., Eison M., Byran K., and Elhson G. (1977) A slow-release silicone pellet for chronic amphetamine administration. Eur. J. Pharmacol. 45, 237–242.

    Article  PubMed  CAS  Google Scholar 

  • Jacobs B. L. and Trulson M. E. (1979) Long-term amphetamine treatment decreases brain serotonin metabolism: Implications for theories of schizophrenia. Science 205, 1295–1297.

    Article  PubMed  Google Scholar 

  • Jacobs B. L., Trulson M. E., and Stern W. C. (1976) An animal model for studying the actions of LSD and related hallucinogens. Science 194, 741–743.

    Article  PubMed  CAS  Google Scholar 

  • Kilbey M. M. and Eilinwood E. H. (1977a) Reverse tolerance to stimulantinduced abnormal behavior. Life Sci. 20, 1063–1076.

    Article  PubMed  CAS  Google Scholar 

  • Kilbey M. M. and Elhnwood E. H. (1977b) Chronic administration of stimulant drugs: Response modification, in Cocuineand Other Stimulants (Ellinwood E. H. and Kilbey M. M., eds.), Plenum, New York, pp. 409–430.

    Google Scholar 

  • Klawans H. L. and Margolin D. I. (1975) Amphetamine-induced dopaminergic hypersensitivity in guinea pigs. Arch. Gen. Psychiat. 32, 725–732.

    PubMed  CAS  Google Scholar 

  • Kleven M. S., Woolverton W., and Seiden L. (1988) Lack of long-term monoamine depletions folowing repeated or continuous exposure to cocaine. Brain Res. Bull. 21, 233–237

    Article  PubMed  CAS  Google Scholar 

  • Kramer J. C. (1969) Introduction to amphetamine abuse. J. Psychedelic Drugs 2, 8–13.

    Google Scholar 

  • Kramer J. C., Gischman V., and Littlefield D. (1967) Amphetamine abuse: Pattern and effects of high doses taken intravenously. J. Am. Med. Assoc. 201, 89–93.

    Article  Google Scholar 

  • Lesko L. M., Pischman M., Javaid J., and Davis J. (1982) Iatrogenous cocaine psychosis. N. Engl. J. Med. 307, 11–53.

    Google Scholar 

  • Lipton J., Zeigler S., Wildins J., and Ellison G. (1991) Silicone pellet for continuous cocaine administration: Heightened late-stage behaviors compared to continuous amphetamine. Pharmacol. Biochem. Behav., in press.

    Google Scholar 

  • McGuire M. T., Raleigh R. J., and Brammer G. L. (1982) Sociopharmacology. Ann. Rev. Pharmacol. Toxicol. 22, 643–661.

    Article  CAS  Google Scholar 

  • Magos L. (1969) Persistence of the effect of amphetamine on stereotyped activity in rats. Eur. J. Phurmacol. 6, 200,201.

    Article  CAS  Google Scholar 

  • Nelson L. and Ellison G. (1978) Enhanced sterotypies after repeated injections but not continuous amphetamines. Neuropharmacology 17, 1081–1084.

    Article  PubMed  CAS  Google Scholar 

  • Nielsen E. and Eliison G. D. (1980) A silicone pellet for long-term continuous administration of amphetamine. Commun. Psychopharmacol. 4, 17–20.

    PubMed  CAS  Google Scholar 

  • Nielsen E., Lee T., and Ellison G. D. (1980a) Following several days of continuous administration d-amphetamine acquires hallucination-like properties. Psychopharmacology 68, 197–200.

    Article  PubMed  CAS  Google Scholar 

  • Nielsen E. B, Neiisen M., Ellison G., and Braestrup E. (1980) Decreased spiroperidol and LSD binding in rat brain after continuous amphetamine. Eur. J. Pharmacol. 66, 14–154.

    Article  Google Scholar 

  • Nwanze E. and Jonsson G. (1981) Amphetamine neurotoxicity on dopamine nerve terminals in the caudate nucleus of mice. Neurosci. Lett. 26, 163–168.

    Article  PubMed  CAS  Google Scholar 

  • Post R. M. (1975) Cocaine psychoses: A continuum model. Am. J. Psychiat. 132, 225–231.

    PubMed  CAS  Google Scholar 

  • Post R. M. (1976) Clinical aspects of cocaine: Assessment of acute and chronic effects in animals and man, in Cocaine: Chemical, Biological, Clinical, Social and Treatment Aspects (Mule S. J., ed.), CRC, Cleveland, pp. 203–215.

    Google Scholar 

  • Post R. M. and Rose H. (1976) Increasing effects with repetitive cocaine administration in the rats. Nature 260, 731,732.

    Article  PubMed  CAS  Google Scholar 

  • Potthoff A. D, EIIison G., and Nelson L. (1983) Ethanol intake increases awareness during continuous administration of amphetamine and nicotine, but not several other drugs. Pharmacol. Biochem. Behav. 18, 489–493.

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte G. A., Schuster C. R., and Seiden L. S. (1980) Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: A regional study. Brain Res. 193, 153–163.

    Article  PubMed  CAS  Google Scholar 

  • Robinson T. and Becker J. (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis. Brain Res. Rev. 11, 157–198.

    Article  CAS  Google Scholar 

  • Ryan L. J., Martone M., Linder J., and Groves P. M. (1988) Cocaine, in contrast to d-amphetamine, does not cause axonal terminal degeneration in neostriatum and agranular frontal cortex of long-evans rats. Life Sci. 43, 1403–1409.

    Article  PubMed  CAS  Google Scholar 

  • Scheel-Kruger J. (1971) Behavioral and biochemical comparison of amphetamine derivatives, cocaine, benztropine and tricyclic antidepressant drugs. Eur. J. Pharmacol. 18, 63–73.

    Article  Google Scholar 

  • Segal D. S. and Mandell A. J. (1974) Long-term administration of d-amphetamine: Progressive augmentation of motor activity and stereotypy. Pharmacol. Biochem. Behav. 2, 249.

    Article  PubMed  CAS  Google Scholar 

  • Segal R. K. (1977) Cocaine: Recreationaluse and intoxication. In Cocaine 1977 (Petersen R. C. and Stillman R. C., eds.), US Government Printing Office, Washington, DC.

    Google Scholar 

  • Slater E. (1959) Amphetamine psychosis. Br Med. J. i, 488.

    Article  Google Scholar 

  • Smith R. C. (1969) The world of the Haight-Ashbury speed freak. J. Psychedelic Drugs 2, 77–83.

    Google Scholar 

  • Snyder S. H., Bannejee S., Yamamura H., and Greenberg D. (1974) Drugs, neurotransmitters and schizophrenia: Phenothiazines, amphetamine and enzymes synthesizing psychotomimetic drugs and schizophrema research. Science 184, 1243–1253.

    Article  PubMed  CAS  Google Scholar 

  • Steranka L. and Sanders-Bush E. (1980) Long-term effects of continuous exposure to amphetamine on brain dopamine concentration and synaptosomal uptake in mice. Eur. J. Pharmacol. 65, 439–443.

    Article  PubMed  CAS  Google Scholar 

  • Stripling J. S. and Ellinwood E. H. (1976) Cocaine: Physiological and behavioral effects of acute and chronic administration, in Cocaine: Chemical, Biological, Chemical, Social and Treatment Aspects (Mule S. J., ed.), CRC, Cleveland.

    Google Scholar 

  • Trulson M. E., Babb S., Joe J., and Raese J. (1986) Chronic cocaine administration depletes tyrosine hydroxylase immunoreactivity in the rat brain nigral striatal system: Quantitative light microscopic studies. Exp. Neurol. 94, 744–756.

    Article  PubMed  CAS  Google Scholar 

  • Waldorf D., Murphy S., Reinarman C., and Joyce B. (1977) Doing Coke: An Ethnography of Users and Sellers (Drug Abuse Council, Washington, DC).

    Google Scholar 

  • Wesson D. R. and Smith D. E. (1977) Cocaine: Its use for central nervous system stimulation including recreational and medical uses, in Cocaine 1977 (Petersen R. C. and Stillman R. C., eds.), US Government Printing Office, Washington, DC.

    Google Scholar 

  • Whitby L. G., Hertting G. G., and Axelrod J. (1960) Effect of cocaine on the disposition of noradrenaline labeled with tritium. Nature l87, 604,605.

    Article  Google Scholar 

  • Wyatt R. (1978). Is there an endogenous amphetamine? A testable hypothesis of schizophrenia, in The Nature of Schizophrenia (Wynne L., Cromwell R., and Matthysse S, eds.), Wiley, New York, pp. 116–125.

    Google Scholar 

  • Young D. and Scoville W. B. (1938) Paranoid psychosis in narcolepsy and the possible danger of Benzedrine TM treatment. Meli. Clin. North Am. 22, 637–646.

    Google Scholar 

  • Zeigler S., Lipton J., Toga A., and Ellison G. (1991) Continuous cocaine administration produces persisting changesin brain neurochemistry and behavior. Brain Res., in press.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1991 The Humana Press Inc.

About this protocol

Cite this protocol

Ellison, G.D. (1991). Animal Models of Hallucinations. In: Boulton, A.A., Baker, G.B., Martin-Iverson, M.T. (eds) Animal Models in Psychiatry, I. Neuromethods, vol 18. Humana Press. https://doi.org/10.1385/0-89603-198-5:151

Download citation

  • DOI: https://doi.org/10.1385/0-89603-198-5:151

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-198-2

  • Online ISBN: 978-1-59259-623-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics