Dopamine Receptors Hypersensitivity: Further Confirmation Following Drug Abuse Model

  • Abraham Flemenbaum
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 90)


Controversial multiple investigations have reported that chronic administration of amphetamine or similar drugs in different animals produces a reverse tolerance or a receptor hypersensitivity. However, most studies utilized large doses given chronically and for lengthy periods of time.

Real life drug abusers tend to utilize drugs in a cyclic pattern of intermittently increasing doses and then “crashing off” depending on the availability of drugs and psychiatric treatment.

In this experiment I intended to demonstrate receptor hypersensitivity with less chronic administration of drugs (in this case only six dosages) given in about two weeks, intermittently, and in increasing dosages to simulate somewhat closer a drug abuse model. I also utilized a lengthier period of time of waiting inbetween the pretreatment and post-treatment evaluation (eight weeks). The subjects were 16 Sprague-Dawley rats of initial weight of 150 – 200 grams, acclimated to photoelectric cell cages. They were given either D- or L-amphetamine in alternating days for two weeks and in increasing dosages. Both activity and stereotype behavior (SB) were measured. The animals were given eight weeks of rest and then retested with a subthreshold dose of the same drug previously utilized and two days later with the smallest dose of the same medication again. The results showed that the latency and the threshold was decreased and the response was maximized but this was statistically true only for SB, as it did not reach statistical significance for hyperactivity

The relationship of this phenomenon of dopamine receptor hypersensitivity and the clinical findings in dyskinetic disorders, is discussed; also some ideas for further research in this area are brought to light.


Dopamine Receptor Drug Abuse Model Subthreshold Dose Dyskinetic Movement Amphetamine Abuse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Costall, B. and Naylor, R.J. (1973). The role of telencephalic dopaminergic systems in the mediation of apomorphine-stereo- types behaviour. Euro. J. Pharm. 24, 8–24.CrossRefGoogle Scholar
  2. Cox, C., Harrison-Read, P.E., Steinberg, H. et at: (1971). Lithium attenuates drug-induced hyperactivity in rats. Nature 232, 336–337.CrossRefPubMedGoogle Scholar
  3. Creese, I. and Iversen, S.D. (1974). The role of forebrain dopamine systems in amphetamine induced stereotyped behavior in the rat. Psychopharmacotogia (Bert.) 39 ,345–357.CrossRefGoogle Scholar
  4. Creese, I. and Iversen, S.D. (1975). The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res. 83 ,419–436.CrossRefPubMedGoogle Scholar
  5. Creese, I., Burt, D.R. and Snyder, S.H. (1975). Dopamine receptor binding: Differentiation of agonist and antagonist states. Life Sci. 17 ,993–1002.CrossRefGoogle Scholar
  6. Creese, I., Burt, D.R. and Snyder, S.H. (1976). DA receptor binding predicts clinical and pharmacological potencies of antischizo- phrenic drugs. Science 192 ,481–483.CrossRefPubMedGoogle Scholar
  7. Davies, C., Sanger, D.J., Steinberg, H., et. at. (1974). Lithium and alpha-Methyl-p-Tyrosine prevent “manic” activity in rodents. Psychopharmacotogia (Bert) 36 ,263–274.CrossRefGoogle Scholar
  8. Eibergen, R.D. and Carlson, K.R. (November 7, 1975). Dyskinesias elicited by Methamphetamine:Susceptibility of former Methadone- consuming monkeys. Science 192 ,588–590.CrossRefGoogle Scholar
  9. Ellinwood, E.H. and Kilbey, M.M. (1975). Amphetamine stereotypy; the influence of environmental factors and prepotent behavioral patterns on its topography and development. Biot. Psychiatry. 10 ,3–16.Google Scholar
  10. Iversen, S.D. and Creese, I. (1975). Behavioral correlates of dopaminergic supersensitivity. In Advances in Neurology. (Caine, D.B., Chase, T.N. and Barbeau, A., Eds.) 9 ,81–92. Raven Press, N.Y.Google Scholar
  11. Klawans, H.L. and Weiner, W.J. (1974). The effect of d-amphetamine on choreiform movement disorders. Neurology 24 ,312–318.CrossRefPubMedGoogle Scholar
  12. Klawans, H.L. Crosset, P. and Dana, N. (1975). Effect of chronic amphetamine exposure on stereotyped behavior: Implications for pathogenesis of L-DOPA-Induced dyskinesias. In Advances in Neurology. (Caine, D.B., Chase, T.N. and Barbeau, A., Eds.) 9 ,105–112. Raven Press, N.Y.Google Scholar
  13. Klawans, H.L. and Margolin, D.I. (1975). Amphetamine-induced dopaminergic hypersensitivity in guinea pigs. Arch. Gen. Psychiat. 32 ,725–732.CrossRefPubMedGoogle Scholar
  14. Kramer, J.C. (1972). Introduction to amphetamine abuse. In Current Concepts on Amphetamine Abuse. National Institute of Mental Health Publication 72-9085 (Ellinwood, E.H. and Cohen, S., Eds.) pp. 177–184. Washington, D.C., U.S. Government Printing Office.Google Scholar
  15. Lal, S. and Sourkes, T.L. (1972). Potentiation and inhibition of the amphetamine stereotype in rats by neuroleptics and other agents. Arch. Int. Pharmacodyn. 199 ,289–301.PubMedGoogle Scholar
  16. Mago, L. (1969). Persistence of the effect of amphetamine on stereotyped activity in rats. Eur. J. Pharmacol. 6 ,200–201.CrossRefGoogle Scholar
  17. Post, R.M. and Kopanda, R.T. (June 1976). Cocaine, Kindling and Psychosis. Am. J. Psychiat. 133 ,627–632.CrossRefPubMedGoogle Scholar
  18. Sayers, A.C., Bürki, H.R., Ruch, W. and Asper, H. (1975). Neuro-leptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesias. Effects of Clozapine, Haloperidol, Loxapine and Chlorpromazine. Psycho pharmacologia 41 ,97–104.CrossRefGoogle Scholar
  19. 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 ,249–255.CrossRefPubMedGoogle Scholar
  20. Segal, D.S. Geyer, M.A. and Wiener, B.E. (25 July 1975). Strain differences during intra-ventricular infusion of norepinphrine: Possible role of receptor sensitivity. Science 189 ,301–303.CrossRefPubMedGoogle Scholar
  21. Tarsy, D. and Baldessarini, R.J. (1974). Behaviour super-sensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines. Neuropharmacology 13 ,927–940.CrossRefPubMedGoogle Scholar
  22. Wolfarth, S., Dulska, E. and Lacki, M. (1974). Corapar ison of the effects of the intranigral injections of cholinomimetics with systemic injections of the dopamine receptor stimulating and blocking agents in the rabbit. Neuropharmacology 13 ,867–875.CrossRefPubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Abraham Flemenbaum
    • 1
  1. 1.Department of PsychiatryTexas Tech University School of MedicineLubbockUSA

Personalised recommendations