Journal of Neural Transmission

, Volume 38, Issue 2, pp 107–122 | Cite as

On the role of dopamine in the pathophysiology of anorexia nervosa

  • Virginia C. Barry
  • H. L. Klawans


Based on a review of the pathophysiology of the major symptoms of anorexia nervosa, it was suggested that increased activity of dopamine at central dopamine receptors plays a role in the pathophysiology of this disorder. Although dopamine receptor site hypersensitivity, or synthesis, of a false transmitter could account for this, a defect in negative feedback control mechanisms is more consistent with the known characteristics of anorexia nervosa. The possible role of pure dopamine antagonists in symptomatic treatment and of dopamine agonists in reversing this disorder was discussed.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anden, N.-E.: Pharmacological and anatomical implications of induced abnormal movements with L-dopa. In: L-dopa and Parkinsonism (Barbeau, A., McDowell, F. H., eds.), pp. 132–143. Philadelphia: F. A. Davis. 1970.Google Scholar
  2. Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol.19, 627 to 629 (1967).Google Scholar
  3. Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur. J. Pharmacol.11, 303–314 (1970).Google Scholar
  4. Baez, L. A.: Role of catecholamines in the anorectic effects of amphetamine in rats. Psychopharmacologia35, 91–98 (1974).Google Scholar
  5. Baldessarini, R. J.: Pharmacology of the amphetamines. Pediatrics49, 694 to 700 (1972).Google Scholar
  6. Barbeau, A., Mars, H., Gillo-Joffroy, L.: Adverse clinical side effects of levodopa therapy. In: Recent Advances in Parkinson's Disease (Barbeau, A., McDowell, F. H., eds.). Philadelphia: F. A. Davis. 1971.Google Scholar
  7. Barnett, A., Goldstein, J., Taber, R. I.: Apomorphine-induced hypothermia in mice, a possible dopaminergic effect. Arch. Int. Pharmacodyn. Ther.198, 242–247 (1972).Google Scholar
  8. Barzaghi, F., Groppetti, A., Mantegazza, P., Muller, E. F.: Reduction of food intake by apomorphine: A pimozide sensitive effect. J. Pharm. Pharmacol.25, 909–911 (1973).Google Scholar
  9. Bell, D. S.: Comparison of amphetamine psychosis and schizophrenia. Br. J. Psychiatry111, 701–707 (1965).Google Scholar
  10. Bell, D. S., Trethowan, N.: Amphetamine addiction and disturbed sexuality. Arch. Gen. Psychiatry4, 74–78 (1961).Google Scholar
  11. Beumont, P. J. V.: Anorexia nervosa in male subjects. Psychother. Psychosom.18, 365–371 (1970).Google Scholar
  12. Beumont, P. J. V., Carr, P. J., Gelder, M. G.: Plasma levels of luteinizing hormone and of immuno-reactive oestrogens (oestradiel) on anorexia nervosa: Response to clomiphene citrate. Psychol. Med.3, 495–501 (1973).Google Scholar
  13. Bliss, E. L., Branch, C. H.: Anorexia Nervosa. Psychosomatic Medicine Monograph 14. New York: Hoeber. 1960.Google Scholar
  14. Bobon, D. P., Janssen, P. A. J., Bobon, J.: The Neuroleptics. Modern Problems of Pharmapsychiatry. Basel: Karger. 1970.Google Scholar
  15. Boyar, R. M., Katz, J., Finkelstein, J. W., Kapen, S., Weiner, H., Weitzman, E. D., Hellman, L.: Anorexia nervosa: Immaturity of the 24-hour leuteinizing hormone secretory pattern. N. Engl. J. Med.291, 861–865 (1974).Google Scholar
  16. Bruch, H.: Anorexia nervosa and its differential diagnosis. J. Nerv. Ment. Dis.141, 555–566 (1966).Google Scholar
  17. Bruch, H.: Anorexia nervosa in the male. Psychosom. Med.33, 31–47 (1971).Google Scholar
  18. Carlsson, A.: Biochemical implications of dopa-induced actions on the central nervous system, with particular reference to abnormal movements. In: L-dopa and Parkinsonism (Barbeau, A., McDowell, F. H., eds.), pp. 205–213. Philadelphia: F. A. Davis. 1970.Google Scholar
  19. Cole, S. O.: Hypothalamic feeding mechanisms and amphetamine anorexia. Psychol. Bull.79, 13–20 (1973).Google Scholar
  20. Corrodi, H., Fuxe, K., Ungerstedt, U.: Evidence for a new type of dopamine receptor stimulating agent. J. Pharm. Pharmacol.23, 989–991 (1971).Google Scholar
  21. Corrodi, H., Garnebo, L.-O., Fuxe, K., Hamberger, B., Ungerstedt, U.: ET-495 and brain catecholamine mechanisms: Evidence for a stimulation of central dopamine neurons. Eur. J. Pharmacol.20, 195–204 (1972).Google Scholar
  22. Crisp, A. H., Toms, D. A.: Primary anorexia nervosa or weight phobia in the male: Report on 13 cases. Br. Med. J.1, 334–338 (1972).Google Scholar
  23. Dally, P. J.: Anorexia Nervosa. London: Heinemann. 1969.Google Scholar
  24. Danowski, T. S., Livstone, E., Gonzales, A. R., Jung, Y., Khurana, R. C.: Fractional and partial hypopituitarism in anorexia nervosa. Hormones5, 105–118 (1972).Google Scholar
  25. Editors: Anorexia nervosa. Br. Med. J.4, 183–184 (1971).Google Scholar
  26. Ellinwood, E. H. J.: Amphetamine psychosis. I. Description of the individuals and the process. J. Nerv. Ment. Dis.144, 273–283 (1967).Google Scholar
  27. Ellinwood, E. H. J.: Amphetamine psychosis. II. Theoretical implications. Int. J. Neuropsychiatry4, 45–54 (1968).Google Scholar
  28. Ellinwood, E. H. J.: Amphetamine psychosis: A multi-dimensional process. Semin. Psychiatry1, 208–226 (1969).Google Scholar
  29. Ellinwood, E. H. J., Sudilovsky, A., Nelson, L. M.: Evolving behavior in the clinical and experimental amphetamine (model) psychosis. Am. J. Psychiatry130, 1088–1093 (1973).Google Scholar
  30. Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia10, 316–323 (1967).Google Scholar
  31. Frazier, S. H.: Anorexia nervosa. Dis. Nerv. Syst.26, 155–159 (1965).Google Scholar
  32. Fuxe, K.: Tools in the treatment of Parkinson's disease: Studies on new types of dopamine receptor stimulating agents. In: Progress in the Treatment of Parkinsonism (Calne, D. B., ed.). New York: Raven Press. 1973.Google Scholar
  33. Fuxe, K., Sjoqvist, F.: Hypothermic effect of apomorphine in the mouse. J. Pharm. Pharmacol.24, 702–705 (1972).Google Scholar
  34. Fuxe, K., Hökfelt, T., Jonsson, G.: Participation of central monoaminergic neurons in the regulation of anterior pituitary secretion. In: Neurochemical Aspects of Hypothalamic Function (Martini, L., Meites, J., eds.), pp. 61–83. London: Academic Press. 1970 a.Google Scholar
  35. Fuxe, K., Hökfelt, T., Ungerstedt, U.: Morphological and functional aspects of central monoamine neurons. In: International Review of Neurobiology (Pfeiffer, C. C., Smythies, J., eds.), pp. 93–126. New York: Academic Press. 1970 b.Google Scholar
  36. Fuxe, K., Agnati, L. F., Corrodi, H., Everitt, B. J., Hökfelt, T., Lofstrom, A., Ungerstedt, U.: Action of dopamine receptor agonists in forebrain and hypothalamus: Rotational behavior, ovulation, and dopamine turnover. In: Advances in Neurology, Vol. 9 (Calne, D. B., Chase, T. N., Barbeau, A., eds.), pp. 223–242. New York: Raven Press. 1975.Google Scholar
  37. Greaves, G.: Sexual disturbances among chronic amphtamine users. J. Nerv. Ment. Dis.155, 363–365 (1972).Google Scholar
  38. Gull, W. W.: The address in Medicine delivered before the Annual Meeting of the British Medical Association at Oxford, Vol.2, pp. 171–176 (1868).Google Scholar
  39. Hart, T., Kase, N., Kimball, C. P.: Induction of ovulation and pregnancy in patients with anorexia nervosa. Am. J. Obstet. Gynecol.108, 508 to 584 (1970).Google Scholar
  40. Hökfelt, T., Fuxe, K.: On the morphology and neuroendocrine role of the hypothalamic catecholamine neurons. In: Brain-Endocrine Interaction. Median Eminence: Structure and Function (Knigge, M., ed.). New York: A. J. Phiebig. 1972.Google Scholar
  41. Johansson, A. J., Knorr, N. J.: Treatment of anorexia nervosa by levodopa. Lancet2, 591 (1974).Google Scholar
  42. Kay, D. W. K., Leigh, D.: The natural history, treatment, and prognosis of anorexia nervosa, based on a study of 38 patients. J. Ment. Sci.100, 411–431 (1954).Google Scholar
  43. Kidd, C. B., Wood, J. F.: Some observations on anorexia nervosa. Postgrad. Med. J.42, 443–448 (1966).Google Scholar
  44. Klawans, H. L.: The pharmacology of tardive dyskinesias. Am. J. Psychiatry130, 82–86 (1973).Google Scholar
  45. Klawans, H. L., Margolin, D. I.: Amphetamine-induced hypersensitivity in guinea pigs (implications in psychosis and human movement disorders). Arch. Gen. Psychiatry32, 725–732 (1975).Google Scholar
  46. Klawans, H. L., Shenker, D. M.: Observations on the dopaminergic nature of hyperthyroid chorea. J. Neural Transm.33, 73–81 (1972).Google Scholar
  47. Klawans, H. L., Weiner, W. J.: Animal models of human extrapyramidal disorders. In: Models of Human Neurological Diseases (Klawans, H. L., ed.), pp. 5–38. Amsterdam: Excerpta Medica. 1974.Google Scholar
  48. Klawans, H. L., Ilahi, M. M., Ringel, S. P.: Toward an understanding of the pathophysiology of Huntington's chorea. Confin. Neurol.33, 297–303 (1971).Google Scholar
  49. Klawans, H. L., Goetz, C. C., Westheimer, R.: Pathophysiology of schizophrenia and the striatum. Dis. Nerv. Syst.33, 714–719 (1973).Google Scholar
  50. Klawans, H. L., Westheimer, R., Goetz, C. C.: A pharmacological model of the pathophysiology of schizophrenia. Dis. Nerv. Syst.36, 267–275 (1975).Google Scholar
  51. Lakoff, K. M., Feldman, J. D.: Anorexia nervosa associated with pregnancy. Obstet. Gynecol.39, 699–701 (1972).Google Scholar
  52. Lapin, I. P., Samsonova, M. L.: Apomorphine induced hypothermia in mice and the effect thereon of adrenergic and serotonergic agents. Farmakol. Toksikol.31, 563 (1968).Google Scholar
  53. Lundberg, P. O., Walinder, J. M., Werner, I., Wide, L.: Effects of thyrotorphin-releasing hormone on plasma levels of TSH, FSH, LH, and GH in anorexia nervosa. Eur. J. Clin. Invest.2, 150–153 (1972).Google Scholar
  54. McCann, S. M., Kalra, P. S., Donoso, A. O., Bishop, W., Schneider, H. P. G., Fawcett, D. P., Krulich, L.: The role of monoamines in the control of gonadotrophin and prolactin secretion. In: Brain-Endocrine Interaction. Median Eminence: Structure and Function (Knigge, M., ed.), pp. 224 to 235. New York: A. J. Phiebig. 1972.Google Scholar
  55. Marshall, J. C., Fraser, T. R.: Amenorrhea in anorexia nervosa: Assessment and treatment with clomiphene citrate. Br. Med. J.4, 590–592 (1971).Google Scholar
  56. Mecklenburg, R. S., Loriaux, D. L., Thompson, R. H., Andersen, A. E., Lipsett, M. B.: Hypothalamic dysfunction in patients with anorexia nervosa. Medicine (Baltimore)53, 147–159 (1974).Google Scholar
  57. Meyerson, B. J.: Monoamines and hormone activated oestrus behavior in the ovariectomized hamster. Psychopharmacologia18, 50–57 (1970).Google Scholar
  58. Russell, G. F. M., Beardwood, C. J.: Amenorrhea in the feeding disorders: Anorexia nervosa and obesity. Psychother. Psychosom.18, 359–364 (1970).Google Scholar
  59. Russell, G. F. M., Loraine, J. A., Bell, E. T., Harkness, R. A.: Gonadotrophin and estrogen excretion in patients with anorexia nervosa. J. Psychosom. Res.9, 79–85 (1965).Google Scholar
  60. Rylander, G.: Psychoses and the punding and choreiform syndromes in addiction to central stimulant drugs. Psychiatr. Neurol. Neurochir.75, 203–212 (1972).Google Scholar
  61. Seidensticker, J. F., Tzagournis, M.: Anorexia nervosa-clinical features and long-term follow-up. J. Chronic Dis.21, 361–367 (1968).Google Scholar
  62. Snyder, S. H.: Catecholamines in the brain as mediators of amphetamine psychosis. Arch. Gen. Psychiatry27, 169–179 (1972).Google Scholar
  63. Starkey, F. A., Lee, R. A.: Menstruation and fertigility in anorexia nervosa. Am. J. Obstet. Gynecol.105, 374–379 (1969).Google Scholar
  64. Stevens, J. R.: An anatomy of schizophrenia. Arch. Gen. Psychiatry29, 177–189 (1973).Google Scholar
  65. Theander, S.: Anorexia nervosa. Acta Psychiatr. Scand. (Suppl.)214, 1 (1970).Google Scholar
  66. Vemura, H., Kobayashi, H.: Effects of dopamine implanted in the median eminence on the estrous cycle of the rat. Endocrinol. Japan18, 91–100 (1971).Google Scholar
  67. Wakeling, A., Russell, G. F. M.: Disturbances in regulation of body temperature in anorexia nervosa. Psychol. Med.1, 30–39 (1970).Google Scholar
  68. Warren, M. P., van de Wiele, R. L.: Clinical and metabolic features of anorexia nervosa. Am. J. Obstet. Gynecol.117, 435–449 (1973).Google Scholar
  69. Wiegelmann, W., Solbach, H. G.: Effects of LH-RF on plasma levels of LH and FSH in anorexia nervosa. Horm. Metab. Res.4, 404 (1972).Google Scholar
  70. Weiner, R. I., Gorski, R. A., Sawyer, C. H.: Hypothalamic catecholamines and pituitary gonadotrophic function. In: Brain-Endocrine Interaction. Median Eminence: Structure and Function (Knigge, M., ed.), pp. 236 to 244. New York: A. J. Phiebig. 1972.Google Scholar
  71. Yehuda, S., Wurtman, R. J.: Release of brain dopamine as the probable mechanism fore the hypothermic effect of d-amphetamine. Nature (Lond.)240, 477–478 (1972).Google Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • Virginia C. Barry
    • 1
  • H. L. Klawans
    • 2
  1. 1.Psychosomatic and Psychiatric InstituteMichael Reese Hospital and Medical CenterChicago
  2. 2.Division of Neurology Michael Reese Hospital and Medical Center and Department of Medicine (Neurology)University of Chicago Pritzker School of MedicineChicagoUSA

Personalised recommendations