Skip to main content
SpringerLink
Log in

Biochemical Evidence for a Role for Endorphins in Mental Illness

  • Chapter
Endorphins and Opiate Antagonists in Psychiatric Research

  • 48 Accesses

Abstract

The widespread loci of endorphin and enkephalin neurons in the central nervous system (Bloom et al., 1978; Watson et al., 1978a), the identification of multiple forms of endorphin receptors (Martin et al., 1976; Kosterlitz and Hughes, 1978) and multiple forms of endorphin precursors (Roberts and Herbert, 1977; Lewis et al., 1980), as well as multiple actions of endorphins in the central nervous system all suggest that endorphins play a major role in brain functioning. Biochemical evidence to be discussed below indicates that endorphins and enkephalins may have dual roles as neurohormones and neurotransmitters. Such evidence as the behavioral responses induced by endorphin administration (Lehmann et al., 1979) and the relationship of endorphin levels in the cerebrospinal fluid to psychiatric diagnoses (Rimon et al., 1980) has led to the suggestion that endorphins may be linked to psychiatric disorders.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aghajanian, G. K., 1978, Tolerance of locus coeruleus neurons to morphine and suppression of withdrawal response by clonidine, Nature (London) 276: 186.

    Article  Google Scholar 

  • Akil, H., Madden, J., Patrick, R. L., and Barchas, J. D., 1976, Stress-induced increase in endogenous opiate peptides: Concurrent analgesia and its partial reversal by naloxone, in: Opiates and Endogenous Opioid Peptides ( H. W. Kosterlitz, ed.), pp. 63–70, Elsevier/North-Holland, Amsterdam.

    Google Scholar 

  • Andén, N. E., 1972, Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptic and anti-acetylcholine drugs, J. Pharm. Pharmacol. 24: 905.

    Article  Google Scholar 

  • Atweh, S. F., and Kuhar, M., 1977, Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla, Brain Res. 124: 53.

    Article  Google Scholar 

  • Biggio, G., and Guidotti, A., 1977, Regulation of cyclic GMP in cerebellum by a striatal dopaminergic mechanism, Nature (London) 265: 240.

    Article  Google Scholar 

  • Biggio, G., Brodie, B. B., Costa, E., and Guidotti, A., 1977, Mechanisms by which diazepam, muscimol and other drugs change the content of cyclic GMP in cerebellar cortex, Proc. Natl. Acad. Sci. USA 74: 3592.

    Article  Google Scholar 

  • Bloom, F., Battenberg, E., Rossier, J., Ling, N., and Guillemin, R., 1978, Neurons containing 3-endorphin in rat brain exist separately from those containing enkephalin: Immunocytochemical studies, Proc. Natl. Acad. Sci. USA 75: 1591.

    Article  Google Scholar 

  • Braestrup, C., Albrechtsen, R., and Squires, R. F., 1977, High densities of benzodiazepines receptors in human cortical area, Nature (London) 269: 702.

    Article  Google Scholar 

  • Bunney, B. S., Walters, J. R., and Roth, R. H., 1973, Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single cell activity, J. Pharmacol. Exp. Ther. 185: 560.

    Google Scholar 

  • Cedarbaum, J. M., and Aghajanian, G. K., 1978, Activation of locus coeruleus neurons by peripheral stimuli: Modulation by a collateral inhibitory mechanism, Life Sci. 23: 1383.

    Article  Google Scholar 

  • Chapman, C. R., and Benedetti, C., 1977, Analgesia following transcutaneous electrical stimulation and its partial reversal by a narcotic antagonist, Life Sci. 21: 1645.

    Article  Google Scholar 

  • Clement-Cormier, Y. C., Kebabian, J. W., and Petzold, G. L., 1974, Dopamine-sensitive adenylate cyclase in mammalian brain: A possible site of action of antipsychotic drugs, Proc. Natl. Acad. Sci. USA 71: 1113.

    Article  Google Scholar 

  • Clouet, D. H., and Ratner, M., 1970, Catecholamine biosynthesis in brains of rats treated with morphine, Science 168: 854.

    Article  Google Scholar 

  • Costa, E., Guidotti, A., Mao, C. G., and Suria, A., 1975, New concepts on the mechanism of action of benzodiazepines, Life Sci. 17: 167.

    Article  Google Scholar 

  • Csontos, K., Rust, M., Höllt, V., Mahr, W., Kromer, W., and Teschemacher, H. J., 1979, Elevated plasma 0-endorphin levels in pregnant women and their neonates, Life Sci. 25: 835.

    Article  Google Scholar 

  • Davis, G. C., Bunney, W. E., Jr., DeFraites, E. G., Kleinman, J. E., van Kammen, D. P., Post, R. M., and Wyatt, R. J., 1977, Intravenous naloxone administration in schizophrenia and affective illness, Science 197: 74.

    Article  Google Scholar 

  • Davis, G. C., Buchsbaum, M. S., van Kammen, D. P., and Bunney, W. E., Jr., 1979, Analgesia to pain stimuli in schizophrenics and its reversal by naltrexone, Psychiatry Res. 1: 61.

    Article  Google Scholar 

  • Deyo, S. N., Swift, R. M., and Miller, R. J., 1979, Morphine and endorphin modulate dopamine turnover in rat median eminence. Proc. Natl. Acad. Sci. USA 76: 3006.

    Article  Google Scholar 

  • Di Chiara, G., Morelli, M., Porceddu, M. L., and Gessa, G. L., 1978, Evidence that nigral GABA mediates behavioral responses elicited by striatal dopamine receptor stimulation, Life Sci. 23: 2045.

    Article  Google Scholar 

  • Duka, T., Wüster, H., and Herz, A., 1980, Benzodiazepines modulate striatal enkephalin levels via a GABAergic mechanism, Life Sci. 26: 771.

    Article  Google Scholar 

  • Dupont, A., Cusan, L., Garon, M., Labrie, F., and Li, C. H., 1977, O-Endorphin: Stimulation of growth hormone release in vivo, Proc. Natl. Acad. Sci. USA 74: 358.

    Article  Google Scholar 

  • Emrich, H. M., Höllt, V., Kissling, W., Fischler, M., Laspe, H., Heinemann, H., von Zerssen, D., and Herz, A., 1979, 3-Endorphin-like immunoreactivity in CSF and plasma of patients with schizophrenia and other neuropsychiatric disorders, Pharmakopsychiatr. Neuro-Psychopharmakol. 12: 269.

    Google Scholar 

  • Green, J. P., and Maayani, S., 1977, Tricyclic antidepressant drugs block histamine H2 receptor in brain, Nature (London) 269: 163.

    Article  Google Scholar 

  • Green, J. P., Johnson, C. L., Weinstein, H., and Maayani, S., 1977, Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide, Proc. Natl. Acad. Sci. USA 74: 5697.

    Article  Google Scholar 

  • Green, J. P., Johnson, C. L., and Weinstein, H., 1978, Histamine as a neurotransmitter, in: Psychopharmacology: A Generation of Progress ( M. A. Lipton, A. DiMascio, and K. F. Killam, eds.), pp. 319–332, Raven Press, New York.

    Google Scholar 

  • Guidotti, A., Toffano, G., and Costa, E., 1978, An endogenous protein modulates the affinity of GABA and benzodiazepine receptors in rat brain, Nature (London) 275: 553.

    Article  Google Scholar 

  • Gunne, L. M., Lindström, L., and Terenius, L., 1977, Naloxone-induced reversal of schizophrenic hallucinations, J. Neural Transm. 40: 13.

    Article  Google Scholar 

  • Henderson, G., Hughes, J. W., and Kosterlitz, H. W., 1978, In vitro release of Leu-and Met-enkephalin from the corpus striatum, Nature (London) 271: 677.

    Article  Google Scholar 

  • Henwood, R. W., and Mazurkiewicz, I. M., 1976, Possible role of brain histamine in morphine addiction, in: The Opiate Narcotics ( A. Goldstein, ed.), pp. 209–210, Pergamon Press, Elmsford, N. Y.

    Google Scholar 

  • Holaday, J. W., and Loh, H. H., 1979, Endorphin—opiate interactions with neuroendocrine systems, in: Neurochemical Mechanisms of Opiates and Endorphins (H. H. Loh and D. H. Ross, eds.), Advances in Biochemical Psychopharmacology, Vol. 20, pp. 227–257, Raven Press, New York.

    Google Scholar 

  • Höllt, V., Müller, O. A., and Fahlbusch, R., 1979, Beta-endorphin in human plasma: Basal and pathologically elevated levels, Life Sci. 25: 37.

    Article  Google Scholar 

  • Höllt, V., Przewlocki, R., Bergmann, M., Haarmann, I., and Duka, T., 1980, Increased biosynthesis of O-endorphin in the pars intermedia of rat pituitaries after long term treatment with haloperiodol, in: Endogenous and Exogenous Opiate Agonists and Antagonists ( E. L. Way, ed.), pp. 325–328, Pergamon Press, Elmsford, N. Y.

    Google Scholar 

  • Hong, J. S., Yang, H.-Y. T., Fratta, W., and Costa, E., 1978, Rat striatal methionine enkephalin content after chronic treatment with cataleptogenic and non-cataleptogenic anti-schizophrenic drugs, J. Pharmacol. Exp. Ther. 205: 141.

    Google Scholar 

  • Hosobuchi, Y., Adams, J. E., and Linchitz, R., 1977, Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone, Science 197: 183.

    Article  Google Scholar 

  • Iwatsubo, K., and Clouet, D. H., 1975, Dopamine-sensitive adenylate cyclase of the caudate nucleus of rata: treated with morphine or haloperidol, Biochem. Pharmacol. 24: 1499.

    Google Scholar 

  • Iwatsubo, K., and Clouet, D. H., 1977, Effect of morphine and haloperidol on the electrical activity of rat nigrostriatal neurons, J. Pharmacol. Exp. Ther. 202: 429.

    Google Scholar 

  • J¢rgensen, A., Fog, R., and Veilis, B., 1979, Synthetic enkephalin analogue in treatment of schizophrenia, Lancet 1: 935.

    Article  Google Scholar 

  • Katz, J. B., and Catravas, G. N., 1976, Cerebellar cyclic GMP levels reduced by morphine and pentobarbital on a dose-and time-dependent basis, Biochem. Pharmacol. 25: 2543.

    Google Scholar 

  • Kebabian, J. W., Petzold, G. L., and Greengard, P., 1972, Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain and its similarity to the “dopamine receptor, ” Proc. Natl. Acad. Sci. USA 69: 2145.

    Article  Google Scholar 

  • Kline, N. S., Li, C. H., Lehmann, H. E., Lajtha, A., Laski, E., and Cooper, T., 1977, (3-Endorphin induced changes in schizophrenic and depressed patients, Arch. Gen. Psychiatry 34: 1111.

    Google Scholar 

  • Kosterlitz, H. W., and Hughes, J., 1978, Development of concepts of opiate receptors and their ligands, in: The Endorphins (E. Costa and M. Trabucchi, eds.), Advances in Biochemical Psychopharmacology, Vol. 18, pp. 31–44, Raven Press, New York.

    Google Scholar 

  • Krieger, D. T., Liotta, A. S., Suda, T., Goodgold, A., and Condon, E., 1979, Human plasma immunoreactive lipotropin and adrenocorticotropin in normal subjects and in patients with pituitary—adrenal disease, J. Clin. Endocrinol. Metab. 48: 566.

    Article  Google Scholar 

  • Kuhar, M. J., Pert, C. B., and Snyder, S. H., 1973, Regional distribution of opiate receptor binding in monkey and human brain, Nature (London) 245: 447.

    Article  Google Scholar 

  • Kurland, A. A., McCabe, L., and Hanlon, T., 1976, Contingent naloxone treatment of the narcotic addict: A pilot study, Int. J. Addict. 11: 131.

    Google Scholar 

  • Kuschinsky, K., and Hornykiewicz, O., 1972, Morphine catalepsy in the rat: Relation to striatal dopamine metabolism, Eur. J. Pharmacol. 19: 119.

    Article  Google Scholar 

  • Lehmann, H., Vasavan Nair, N. P., and Kline, N. S., 1979, 13-Endorphin and naloxone in psychiatric patients: Clinical and biological effects, Am. J. Psychiatry 136: 762.

    Google Scholar 

  • Lewis, R. V., Stein, A. S., Kimura, S., Stein, S., and Udenfriend, S., 1980, Enkephalin biosynthetic pathway: Proteins of 8000 and 14000 daltons in the bovine adrenal gland, Proc. Natl. Acad. Sci. USA 77: 5018.

    Article  Google Scholar 

  • Lloyd, K. G., Stadler, H., and Bartholini, G., 1973, Dopamine and acetylcholine neurons in striatal and limbic structures: Effects of neuroleptic drugs, in: Frontiers in Catecholamine Research ( E. Usdin and S. H. Snyder, eds.), pp. 777–779, Pergamon Press, Elmsford, N.Y.

    Google Scholar 

  • Loh, H. H., Tseng, L. F., and Wei, E., 1976, I3-Endorphin is a potent analgesic agent, Proc. Natl. Acad. Sci. USA 73: 2895.

    Article  Google Scholar 

  • Mao, C. G., Guidotti, A., and Costa, E., 1975, Inhibition by diazepam of the tremor and the increase of cerebellar cGMP content elicited by harmaline, Brain Res. 83: 516.

    Article  Google Scholar 

  • Marchand, W. E., Sarota, B., Marble, H. C., Leary, T. M., Burbank, C. B., and Bellinger, M. J., 1969, Occurrence of painless acute surgical disorders in psychotic patients, N. Engl. J. Med. 260: 580.

    Article  Google Scholar 

  • Marco, E., Mao, C. G., Cheney, D. L., Revuelta, A., and Costa, E., 1976, The effects of antipsychotics on the turnover rate of GABA and acetylcholine in rat brain nuclei, Nature (London) 264: 363.

    Article  Google Scholar 

  • Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E., and Gilbert, P. E., 1976, The effects of morphine-and nalorphine-like drugs in the non-dependent and morphine-dependent chronic spinal dog, J. Pharmacol. Exp. Ther. 197: 517.

    Google Scholar 

  • Mayer, D. J., Price, D. D., and Rafii, A., 1977, Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone, Brain Res. 121: 368.

    Article  Google Scholar 

  • Meites, J., Bruni, J. F., Van Vugt, D. A., and Smith, A. F., 1979, Relation of endogenous opioid peptides and morphine to neuroendocrine functions, Life Sci. 24: 1325.

    Article  Google Scholar 

  • Moroni, F., Cheney, D. L., and Costa, E., 1978, The turnover rate of acetylcholine in brain nuclei of rats injected intraventricularly and intraseptally with alpha-and beta-endorphin, Neuropharmacology 17: 191.

    Article  Google Scholar 

  • Moroni, F., Peralta, E., Cheney, D. L., and Costa, E., 1979, On the regulation of yaminobutyric acid neurons in caudatus, pallidus and nigra: Effects of opioids and dopamine agonists, J. Pharmacol. Exp. Ther. 208: 190.

    Google Scholar 

  • Nakai, Y., Nakao, K., Oki, S., Imura, H., and Li, C. H., 1978, Presence of immunoreactive 13-endorphin in plasma of patients with Nelson’s syndrome and Addison’s disease, Life Sci. 23: 2293.

    Article  Google Scholar 

  • Nedopil, N., and Wither, E., 1979, Effects of the synthetic analogue of methionine enkephalin FK 33–824 on psychotic symptoms, Pharmakopsychiatr. Neuro-Psychopharmakol. 12: 277.

    Google Scholar 

  • Paul, S. M., Syapin, P. J., Paugh, B., Moncada, V., and Skolnick, P., 1979, Correlation between benzodiazepine receptor occupation and anticonvulsant effects of diazepam, Nature (London) 281: 688.

    Article  Google Scholar 

  • Peroutka, S. J., U’Prichard, D. C., Greenberg, D. A., and Snyder, S. H., 1977, Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain, Neuropharmacology 16: 549.

    Article  Google Scholar 

  • Racagni, G., Cheney, D. L., Zsilla, G., and Costa, E., 1976, The measurement of acetylcholine turnover rate in brain structures, Neuropharmacology 15: 723.

    Article  Google Scholar 

  • Richelson, E., 1978, Tricyclic antidepressants block histamine HI receptors of mouse neuroblastoma cells, Nature (London) 274: 176.

    Article  Google Scholar 

  • Rimon, R., Terenius, L., and Kampman, R., 1980, Cerebrospinal fluid endorphins in schizophrenia, Acta Psychiatr. Scand. 61: 395.

    Google Scholar 

  • Roberts, J. L., and Herbert, E., 1977, Characterization of a common precursor to corticotropin and 3-lipotropin: Identification of 3-lipotropin peptides and their arrangement relative to corticotropin in the precursor synthesized in a cell-free system, Proc. Natl. Acad. Sci. USA 74: 5300.

    Article  Google Scholar 

  • Salzmann, B., and Frosch, W. A., 1972, Methadone maintenance for the psychiatrically disturbed, Natl. Conf. Meth. Treat. Prog. 4: 117.

    Google Scholar 

  • Schwartz, J. C., Costentin, J., Martres, M. P., Protais, P., and Baudry, M., 1978, Review: Modulation of receptor mechanisms in the central nervous system: Hyper-and hypo-sensitivity to catecholamines, Neuropharmacology 17: 665.

    Article  Google Scholar 

  • Smith, C. B., Sheldon, M. I., Bednarczyk, J. H., and Villarreal, J. E., 1972, Morphine-induced increases in the incorporation of 14C-tyrosine into 14C-dopamine and ‘4C-norepinephrine in the mouse brain: Antagonism by naloxone and tolerance, J. Pharmacol. Exp. Ther. 180: 547.

    Google Scholar 

  • Suria, A., and Costa, E., 1973, Benzodiazepines and posttetanic potentiation in sympathetic ganglia of the bullfrog, Brain Res. 50: 235.

    Article  Google Scholar 

  • Tallman, J. F., Paul, S. M., Skolnick, P., and Gallager, D. W., 1980, Receptors for the age of anxiety: Pharmacology of the benzodiazepines, Science 207: 274.

    Article  Google Scholar 

  • Terenius, L., Wahlström, A., Lindström, L. H., and Widerlöv, E., 1976, Increased CSF levels of endorphins in chronic psychosis, Ncurosci. Lett. 3: 157.

    Google Scholar 

  • Teschemacher, H., Breidenbach, T., König, A., Luckhardt, M., and Davies-Osterkamp, S., 1980, Plasma levels of I3-endorphin and 3-lipotropin in humans under stress, in: Endogenous and Exogenous Opiate Agonists and Antagonists ( E. L. Way, ed.), pp. 307–308, Pergamon Press, Elmsford, N. Y.

    Google Scholar 

  • Tran, V. T., Chang, R. S. L., and Snyder, S. H., 1978, Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramine, Proc. Natl. Acad. Sci. USA 75: 6290.

    Article  Google Scholar 

  • U’Prichard, D. C., Greenberg, D. A., Sheehan, P. P., and Snyder, S. H., 1978, Tricyclic antidepressants: Therapeutic properties and affinity for a-noradrenergic receptor binding sites in the brain, Science 199: 197.

    Article  Google Scholar 

  • Van Loon, G. R., and Kim, C., 1978, Beta-endorphin-induced increase in striatal dopamine turnover, Life Sci. 23: 961.

    Article  Google Scholar 

  • Van Vugt, D. A., Bruni, J. F., Sylvester, P. W., Chen, H. T., Ieira, T., and Meites, J., 1979, Interaction between opiates and hypothalamic dopamine on prolactin release, Life Sci. 24: 2361.

    Article  Google Scholar 

  • Verebey, K., Volavka, J., and Clouet, D. H., 1978, Endorphins in psychiatry: An overview and a hypothesis, Arch. Gen. Psychiatry 35: 877.

    Article  Google Scholar 

  • Volavka, J., Mallya, A., Baig, S., and Perez-Cruet, J., 1977, Naloxone in chronic schizophrenia, Science 196: 1227.

    Article  Google Scholar 

  • Waterfield A. A., Smokcum, R. W., Hughes, J., Kosterlitz, H. W., and Henderson, G., 1977, In vitro pharmacology of the opioid peptides, enkephalins and endorphins, Eur. J. Pharmacol. 143: 107.

    Article  Google Scholar 

  • Watson, S. J., Akil, H., Richard, C. W., III, and Barchas, J. D., 1978a, Evidence for two separate opiate peptide neuronal systems, Nature (London) 275: 226.

    Article  Google Scholar 

  • Watson, S. J., Berger, P. A., Akil, H., Mills, M. J., and Barchas, J. D., 1978b, Effects of naloxone on schizophrenia: Reduction in hallucinations in a subpopulation of subjects, Science 201: 73.

    Article  Google Scholar 

  • Wei, E., and Loh, H. H., 1976, Physical dependence on opiate-like peptides, Science 193: 1262.

    Article  Google Scholar 

  • Westerink, B. H., and Korf, J., 1975, Influence of drugs on striatal and limbic homovanillic acid concentration in the rat brain, Eur. J. Pharmacol. 33: 31.

    Article  Google Scholar 

  • Wilson, S. P., Chang, K. J., and Viveros, O. H., 1980, Synthesis of enkephalins by adrenal medullary chromaffin cells—Reserpine increases incorporation of radiolabeled amino acids, Proc. Natl. Acad. Sci. USA 77: 4364.

    Article  Google Scholar 

  • Zieglgänsberger, W., Siggins, G., French, E., and Bloom, F., 1978, Effects of opioids on single unit activity, in: Characteristics and Function of Opioids ( J. M. van Ree and L. Terenius, eds.), pp. 75–86, Elsevier/North-Holland, Amsterdam.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. New York State Division of Substance Abuse Services Research Laboratory, Downstate Medical Center, Brooklyn, New York, USA

    Doris H. Clouet

Authors
  1. Doris H. Clouet
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. William S. Hall Psychiatric Institute, Department of Neuropsychiatry and Behavioral Sciences, Department of Pharmacology, University of South Carolina School of Medicine, Columbia, South Carolina, USA

    Nandkumar S. Shah Ph.D. (Chief of Research Services, Research Professor, Adjunct Professor) (Chief of Research Services, Research Professor, Adjunct Professor)

  2. William S. Hall Psychiatric Institute, Department of Neuropsychiatry and Behavioral Sciences, University of South Carolina School of Medicine, Columbia, South Carolina, USA

    Alexander G. Donald M.D. (Director, Professor and Chairman) (Director, Professor and Chairman)

Rights and permissions

Reprints and permissions

Copyright information

© 1982 Plenum Publishing Corporation

About this chapter

Cite this chapter

Clouet, D.H. (1982). Biochemical Evidence for a Role for Endorphins in Mental Illness. In: Shah, N.S., Donald, A.G. (eds) Endorphins and Opiate Antagonists in Psychiatric Research. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1119-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-1119-5_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-1121-8

  • Online ISBN: 978-1-4684-1119-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation