Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-09T09:14:48.410Z Has data issue: false hasContentIssue false
  • English
  • Français

Neuroendocrine Effects of Apomorphine: Characterization of Response Patterns and Application to Schizophrenia Research

Published online by Cambridge University Press:  29 January 2018

John Rotrosen ,
Burton Angrist ,
Samuel Gershon ,
Jeanne Paquin ,
Laura Branchey ,
Marvin Oleshansky ,
Frieda Halpern  and
Edward J. Sachar
John Rotrosen
Affiliation:
Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA
Burton Angrist
Affiliation:
Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA
Samuel Gershon
Affiliation:
Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA
Jeanne Paquin
Affiliation:
Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA
Laura Branchey
Affiliation:
Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA
Marvin Oleshansky
Affiliation:
Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA
Frieda Halpern
Affiliation:
New York State Psychiatric Institute, 722 West 168th Street, New York, New York 10032, USA
Edward J. Sachar
Affiliation:
New York State Psychiatric Institute, 722 West 168th Street, New York, New York 10032, USA
Get access Rights & Permissions [Opens in a new window]

Summary

Apomorphine, a direct-acting dopamine agonist, stimulates release of growth hormone (hGH) and suppresses release of prolactin (PRL) from the anterior pituitary. Previous studies comparing the magnitude of these responses in schizophrenics and controls suggest that many acute (and some chronic) schizophrenics have exaggerated hGH responses; many chronic schizophrenics (and patients with tardive dyskinesia) have blunted hGH responses to apomorphine, and possibly blunted PRL responses. The present studies extend and confirm these findings in chronic schizophrenics; in addition, several studies were undertaken to further characterize these apomorphine-induced endocrine responses. Studies in which apomorphine was given on 2 or 3 separate occasions to each of five subjects indicate that the hGH response is a highly reproducible individual index, but PRL suppression is a less satisfactory measure. hGH responses to apomorphine were consistently antagonized by pretreatment with haloperidol, supporting the concept that the hGH-releasing effect of apomorphine is mediated by its action on dopamine receptors. Cyproheptadine pretreatment was associated with erratic increases or decreases in the hGH response to apomorphine, but did not alter PRL levels or apomorphine-induced PRL suppression. The relationship of these findings to biological hypotheses of schizophrenia and to neuroleptic-induced receptor changes is discussed.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 135 , Issue 5 , November 1979 , pp. 444 - 456
Copyright
Copyright © Royal College of Psychiatrists, 1979 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abdulla, Y. H. & Hamadah, K. (1975) Effect of ADP on PGE1 formation in blood platelets from patients with depression, mania and schizophrenia. British Journal of Psychiatry, 127, 591–5.CrossRefGoogle ScholarPubMed
Aghajanian, G. K. & Wang, R. Y. (1978) Physiology and pharmacology of central serotonergic neurons. In Psychopharmacology: A Generation of Progress (eds. Lipton, M. A., DiMascio, A. and Killam, K. F.). New York: Raven Press.Google Scholar
Anden, N. E., Rubenson, A., Fuxe, K. & Hokfelt, T. (1967) Evidence for dopamine receptor stimulation by apomorphine. Journal of Pharmacy and Pharmacology, 19, 627–9.Google Scholar
Brown, W. A. & Heninger, G. (1976) Stress-induced growth hormone release: psychologic and physiologic correlates. Psychosomatic Medicine, 38, 145–7.CrossRefGoogle ScholarPubMed
Camanni, F., Massara, F., Belforte, L. & Molinatti, G. M. (1975) Changes in plasma growth hormone levels in normal and acromegalic subjects following administration of 2-Br-α-ergocryptine. Journal of Clinical Endocrinology and Metabolism, 40, 363–6.Google Scholar
Carlsson, A. (1978) Antipsychotic drugs, neurotransmitters and schizophrenia. American Journal of Psychiatry, 135, 164–73.Google Scholar
Cooper, R. H., McPherson, M. & Schofield, J. G. (1972) The effect of prostaglandins on ox pituitary content of adenosine 3′:5′-cyclic monophosphate and the release of growth hormone. Biochemical Journal, 127, 143–54.Google Scholar
Dupont, A. Cusan, L., Labrie, F., Coy, D. H. & Li, C. H. (1977) Stimulation of prolactin release in the rat by intraventricular injection of β-endorphin and methionine-enkephalin. Biochemical and Biophysical Research Communications, 75, No. 1, 76–82.Google Scholar
Ernst, A. M. (1967) Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berlin), 10, 316–23.Google Scholar
Ettigi, P., Nair, N. P. V., Lal, S., Cervantes, P. & Guyda, H. (1976) Effect of apomorphine on growth hormone and prolactin secretion in schizophrenic patients, with or without oral dyskinesia, withdrawn from chronic neuroleptic therapy. Journal of Neurology, Neurosurgery and Psychiatry, 39, 870–6.Google Scholar
Feighner, J. P., Robins, E., Guze, S. B., Woodruff, R. A., Winokur, G. & Munoz, R. (1972) Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry, 26, 57–63.Google Scholar
Friend, W. C., Brown, G. M., Jawahir, G., Lee, T. & Seeman, P. (1978) Effect of haloperidol and apomorphine treatment on dopamine receptors in pituitary and striatum. American Journal of Psychiatry, 135: 7, 839–41.Google Scholar
Gala, R. R., Peters, J. A., Pieper, D. R. & Campbell, M. D. (1978) Influence of adrenergic antagonists and apomorphine on prolactin release induced by serotonergic antagonists in the monkey. Life Sciences, 22, 25–30.Google Scholar
Gala, R. R., Subramanian, M. G., Peters, J. A. & Pieper, D. (1977) The effects of serotonergic and adrenergic receptor antagonists on prolactin release in the monkey. Life Sciences, 20, 631–8.Google Scholar
Genazzani, A. R., Lemarchand-Beraud, Th., Aubert, M. L. & Felber, J. P. (1975) Pattern of plasma ACTH, hGH and Cortisol during menstrual cycle. Journal of Clinical Endocrinology and Metabolism, 41, 431–7.Google Scholar
Grandison, L. & Guidotti, A. (1977) Regulation of prolactin release by endogenous opiates. Nature, 270, 357.CrossRefGoogle ScholarPubMed
Gruen, P. H., Sachar, E. J., Langer, G., Altman, N., Leifer, M., Frantz, A. & Halpern, F. (1978) Prolactin responses to neuroleptics in normal and schizophrenic subjects. Archives of General Psychiatry, 35, 108–16.Google Scholar
Horrobin, D. F. (1977) Schizophrenia as a prostaglandin deficiency disease. Lancet, 936–7. April 30.Google Scholar
Imura, H., Kato, Y., Ikeda, M., Morimoto, M., Yawata, M. & Fukase, M. (1968) Increased plasma levels of growth hormone during infusion of propranolol. Journal of Clinical Endocrinology and Metabolism, 28, 1079–81.Google Scholar
Imura, H., Nakai, Y. & Yoshimi, T. (1973) Effect of 5-hydroxytryptophan (5–HTP) on growth hormone and ACTH release in man. Journal of Clinical Endocrinology and Metabolism, 36, 204–6.Google Scholar
Ito, H., Momose, G., Katayama, T., Takagishi, H., Ito, L., Nakajima, H. & Takei, Y. (1971) Effect of prostaglandin on the secretion of human growth hormone. Journal of Clinical Endocrinology and Metabolism, 32, 857–9.CrossRefGoogle ScholarPubMed
Janssen, P. A. J., Neimegeers, C. J. E. & Schellekens, K. H. L. (1965) Is it possible to predict the clinical effects of neuroleptic drugs (major tranquilizers) from animal data: Part I: ‘Neuroleptic activity spectra’ for rats. Arzneimittel-Forschung, 15, 104–10.Google Scholar
Kafka, M. S. & Van Kammen, D. P. (1978) Reduced cAMP production in schizophrenia. Presented at 131st Annual Meeting of the American Psychiatric Association, Atlanta, Georgia, May.Google Scholar
Lal, S., de la Vega, C. E., Sourkes, T. L. & Friesen, H. G. (1973) Effect of apomorphine on growth hormone, prolactin, luteinizing hormone and follicle stimulating hormone levels in human serum. Journal of Clinical Endocrinology and Metabolism, 37, 719–24.Google Scholar
Lal, S., Martin, J. B., de la Vega, C. E. & Friesen, H. G. (1975a) Comparison of the effect of apomorphine and 1-DOPA on serum growth hormone levels in normal men. Clinical Endocrinology, 4, 277–85.Google Scholar
Lal, S., Tolis, G., Martin, J. B., Brown, G. M. & Guyda, H. (1975b) Effect of clonidine on growth hormone, prolactin, luteinizing hormone, follicle stimulating hormone and thyroid stimulating hormone in the serum of normal men. Journal of Clinical Endocrinology and Metabolism, 41, 827–32.Google Scholar
Lal, S., Guyda, H. & Bikadoroff, S. (1977) Effect of methysergide and pimozide on apomorphine-induced growth hormone secretion in men. Journal of Clinical Endocrinology and Metabolism, 44, 766–70.Google Scholar
Langer, G., Sachar, E. J., Halpern, F. S. & Gruen, P. H. (1977) The prolactin response to neuroleptic drugs. A test of dopaminergic blockade: neuroendocrine studies in normal men. Journal of Clinical Endocrinology and Metabolism, 45, 996–1002.CrossRefGoogle ScholarPubMed
Laue, K., Gottlieb, C. W. & Herbert, V. (1966) Preliminary report on coated charcoal immunoassay of human chorionic ‘growth hormone-prolactin’ and growth hormone. Proceedings of the Society of Experimental Biology and Medicine, 123, 126–31.Google Scholar
Maany, I., Frazer, A. & Mendels, J. (1975) Apomorphine: effect on growth hormone. Journal of Clinical Endocrinology and Metabolism, 40, 162–3.Google Scholar
Martin, J. B. (1973) Neural regulation of growth hormone secretion. New England Journal of Medicine, 288, 1384–93.Google Scholar
Matthysse, S. (1973) Antipsychotic drug actions: a clue to the neuropathology of schizophrenia? Federation Proceedings, 32, 200–5.Google Scholar
McLeod, R. M. (1976) Regulation of prolactin secretion. In Frontiers in Neuroendocrinology, Vol. 4 (eds. Martini, L. and Ganong, W. F.). New York: Raven Press.Google Scholar
Meltzer, H. Y., Goode, D. J. & Fang, V. S. (1978a) The effect of psychotropic drugs on endocrine function. I. Neuroleptics, precursors, and agonists. In Psychopharmacology: A Generation of Progress (eds. Lipton, M. A., DiMascio, A. and Killam, K. F.). New York: Raven Press.Google Scholar
Meltzer, H. Y., Sachar, E. J. & Frantz, A. G. (1974) Serum prolactin levels in unmedicated schizophrenic patients. Archives of General Psychiatry, 31, 564–9.Google Scholar
Meltzer, H. Y., Simonovic, M., Fang, V., Pijakalamala, S. & Young, M. (1978b) A comparison of the effects of anti-psychotic drugs on pituitary, striatal and limbic system post-synaptic dopamine receptors. Life Sciences, 23, 605–10.Google Scholar
Mendelson, W. B., Jacobs, L. S., Reichman, J. D., Othmer, E., Cryer, P. E., Trivedi, B. & Daughaday, W. H. (1975) Methysergide suppression of sleep-related prolactin secretion and enhancement of sleep-related growth hormone secretion. Journal of Clinical Investigation, 56, 690–7.Google Scholar
Müller, E. E., Brambilla, F., Cavagnini, F., Peracchi, M. & Panevai, A. (1974) Slight effect of l-tryptophan on growth hormone release in normal human subjects. Journal of Clinical Endocrinology and Metabolism, 39, 1–5.CrossRefGoogle ScholarPubMed
Ojeda, S. R., Jameson, H. E. & McCann, S. M. (1978) Effects of indomethacin and prostaglandin injections on plasma prolactin and growth hormone levels in rats. Endocrinology, 102, 531–9.Google Scholar
Pandey, G. N., Garver, D. L., Hengeveld, C., Erickson, S., Gosenfeld, L. & Davis, J. (1977) Postsynaptic supersensitivity in schizophrenia. American Journal of Psychiatry, 134, 518–22.Google Scholar
Plotnick, L. P., Thompson, R. G., Kowarski, A., Lacerda, L., Migeon, C. & Buzzard, R. (1975) Circadian variation of integrated concentration of growth hormone in children and adults. Journal of Clinical Endocrinology and Metabolism, 40, 240–7.Google Scholar
Rotrosen, J., Angrist, B. M., Gershon, S., Sacher, E. J., & Halpern, F. S. (1976) Dopamine receptor alteration in schizophrenia: neuroendocrine evidence. Psychopharmacology, 51, 1–7.CrossRefGoogle ScholarPubMed
Rotrosen, J., Angrist, B. M., Clark, C., Gershon, S., Halpern, F. & Sachar, E. (1978a) Suppression of prolactin by dopamine agonists in schizophrenics and controls. American Journal of Psychiatry, 135, 949–51.Google Scholar
Rotrosen, J., Angrist, B. M. & Paquin, J. (1978b) Neuroendocrine studies with dopamine agonists in schizophrenia. Psychopharmacology Bulletin, 14, 14–17.Google ScholarPubMed
Rotrosen, J., Miller, A., Mandio, D., Traficante, L. & Gershon, S. (1978c) Reduced PGE1-stimulated 3H-cAMP accumulation in platelets from schizophrenics. Life Sciences, 23, 1989–96.Google Scholar
Sachar, E. J. (1978) Neuroendocrine responses to psychotropic drugs. In Psychopharmacology: A Generation of Progress (eds. Lipton, M. A., DiMascio, A. and Killam, K. F.). New York: Raven Press.Google Scholar
Siegel, S. (1956) Non-parametric Statistics for the Behavioural Sciences. New York: McGraw-Hill, pp. 47–52, 127–136.Google Scholar
Simonovic, M., Meltzer, H. Y. & Fang, V. S. (1978) The effect of GABA and muscimol on plasma prolactin in male rats. Federation Proceedings, 37, Abstract 1795.Google Scholar
Sinha, Y. N., Selby, F. W., Lewis, U. J. & Vander Lann, W. P. (1973) A homologous radioimmunoassay for human prolactin. Journal of Clinical Endocrinology and Metabolism, 36, 509–16.Google Scholar
Smythe, G. A. & Lazarus, L. (1974) Suppression of human growth hormone secretion by melatonin and cyproheptadine. Journal of Clinical Investigation, 54, 116–21.Google Scholar
Snyder, S. H., Banerjee, S. P., Yamamura, H. I. & Greenberg, D. (1974) Drugs, neurotransmitters and schizophrenia. Science, 184, 1243–53.CrossRefGoogle ScholarPubMed
Spitzer, R. L., Endicott, J. & Robins, E. (1977) Research Diagnostic Criteria for a Selected Group of Functional Disorders, 3rd edition.CrossRefGoogle Scholar
Stone, C. A., Wenger, H. C., Ludden, C. T., Stavorski, J. M. & Ross, C. A. (1961) Antiserotonin-anti-histaminic properties of cyproheptadine. Journal of Pharmacology and Experimental Therapeutics, 131, 73–84.Google Scholar
Tamminga, C. A., Smith, R. C., Pandey, G., Frohman, L. A. & Davis, J. M. (1977) A neuroendocrine study of supersensitivity in tardive dyskinesia. Archives of General Psychiatry, 34, 1199–1203.Google Scholar
Thorner, M. O., Kirk, C. R. & MacLeod, R. M. (1978) Alcohol stimulation of prolactin release from perfused isolated rat pituitary cells. Federation Proceedings, 37, Abstract 2229.Google Scholar
Van Vugt, D. A., Bruni, J. F. & Meites, J. (1978) Naloxone inhibition of stress-induced increase in prolactin secretion. Life Sciences, 22, 85–90.Google Scholar
Vijayan, E. & McCann, S. M. (1978) Involvement of gamma-aminobutyric acid in the control of gonadotropin and prolactin release in conscious female rats. Federation Proceedings, 37, Abstract 1796.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.