Skip to main content
SpringerLink
Log in

Naloxone effects on β-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

8 mg of naloxone were administered IV to 14 normal volunteers in a placebo-controlled, double-blind experiment. Plasma levels of β-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG were determined before and 45 min after administration. Naloxone elicited significant increases in cortisol and MHPG but did not change plasma levels of the other compounds. In an additional experiment on two subjects, 20 mg of naloxone caused elevations of β-endorphin as well as of cortisol. This parallel increase indicates that the linkage between the secretion of β-endorphin and ACTH/cortisol may be dose-dependent. The increase in MHPG is in agreement with the hypothesized association of noradrenergic hyperactivity and opiate withdrawal.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alper RH, Demarest KT, Moore KE (1980) Morphine differentially alters synthesis and turnover of dopamine in central neuronal systems. J Neural Transm 48:157–165

    Google Scholar 

  • Berger PA, Watson SJ, Akil H, Elliott H, Rubin RT, Pfefferbaum A, Davis KL, Barchas JD, Li CH (1980) β-endorphin and schizophrenia. Arch Gen Psychiatry 37:635–640

    Google Scholar 

  • Bergmann F, Altstetter R, Weissmann BA (1978) In vivo interaction of morphine and endogenous opiate-like peptides. Life Sci 23:2601–2608

    Google Scholar 

  • Bird SJ, Kuhar MJ (1977) Iontophoretic application of opiates to the locus coeruleus. Brain Res 122:523–533

    Google Scholar 

  • Blank MS, Panerai AE, Friesen HG (1979) Opioid peptides modulate luteinizing hormone secretion during sexual maturation. Science 203:1129–1131

    Google Scholar 

  • Bruni JF, Van Vugt D, Marshall S, Meites J (1977) Effects of naloxone, morphine and methionine enkephalin on serum prolactin, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone and growth hormone. Life Sci 21:461–466

    Google Scholar 

  • Cicero TJ, Schainker BA, Meyer ER (1979) Endogenous opioids participate in the regulation of the hypothalamic-pituitaryluteinizing hormone axis and testosterone's negative feedback control of luteinizing hormone. Endocrinology 104:1286–1291

    Google Scholar 

  • Cocchi D, Santagostino A, Gil-Ad I, Ferri S, Muller EE (1977) Leuenkephalin-stimulated growth hormone and prolactin release in the rat: comparison with the effect of morphine. Life Sci 20:2041–2046

    Google Scholar 

  • Cusan L, Dupont A, Kledzik GS, Labrie F, Coy DH, Schally AV (1972) Potent prolactin and growth hormone releasing activity of more analogues of met-enkephalin. Nature 268:544–547

    Google Scholar 

  • Deyo SN, Swift RM, Miller RJ (1979) Morphine and endomorphins modulate dopamine turnover in rat median eminence. Proc Natl Acad Sci USA 76:3006–3009

    Google Scholar 

  • Dupont A, Cusan L, Garon M, Labrie F, Li CH (1977) β-endorphin: stimulation of growth hormone release in vivo. Proc Natl Acad Sci USA 74:358–359

    Google Scholar 

  • Eidelberg E (1976) Possible actions of opiates upon synapses. Prog Neurobiol 6:81–102

    Google Scholar 

  • Eisenberg RM (1980) Effects of naloxone on plasma corticosterone in the opiate-naive rat. Life Sci 26:935–943

    Google Scholar 

  • Elchisak MA, Polinsky RJ, Ebert MH, Modlin LT, Kopin IJ (1979) Kinetics of homovanillic acid and determination of its production rate in the rhesus monkey. Life Sci 24:1493–1502

    Google Scholar 

  • Farmer RW, Pierce CE (1974) Plasma cortisol determination: radioimmunoassay and competitive protein binding compared. Clin Chem 20:411–414

    Google Scholar 

  • Ferland, L., Fuxe K, Eneroth P, Gustafsson JA, Skett P (1977) Effects of methionine-enkephalin on prolactin release and catecholamine levels and turnover in the median eminence. Eur J Pharmacol 43:89–90

    Google Scholar 

  • Foley KM, Kourides JA, Inturris CE, Kaiko RE, Zaoulis CG, Posner JB, Houde RW, Li CH (1979) β-endorphin: analgesic and hormonal effects in humans. Proc Natl Acad Sci USA 76:5377–5381

    Google Scholar 

  • Fuxe K, Andersson, K, Hökfelt T, Mutt V, Ferland L, Agnati LF, Granten D, Sad S, Eneroth P, Gustafsson JA (1979) Localization and possible function of peptidergic neurons and their interactions with catecholamine neurons, and the central actions of gut hormones. Fed Proc 38:2333–2340

    Google Scholar 

  • Gold MS, Redmond DE Jr, Donabedian RK (1978a) Prolactin secretion, a measurable central effect of opiate-receptor antagonists. Lancet I:323–324

    Google Scholar 

  • Gold MS, Redmond DE Jr, Kleber HD (1978b) Clonidine blocks acute opiate-withdrawal symptoms. Lancet II:599–601

    Google Scholar 

  • Gudelsky GA, Porter JC (1979) Morphine- and opioid peptide-induced inhibition of the release of dopamine from tuberoinfundibular neurons. Life Sci 25:1697–1702

    Google Scholar 

  • Guillemin R, Vargo T, Rossier J, Minick S, Ling N, Rivier C, Vale W, Bloom F (1977) β-Endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science 197:1367–1369

    Google Scholar 

  • Hart IC, Cowie AT (1978) Effect of morphine, naloxone and an enkephalin analogue on plasma prolactin, growth hormone, insulin and thyroxine in goats. J Endocrinol 77:16p-17p

    Google Scholar 

  • Holaday JW, Loh HH (1979) Endorphin-opiate interactions with neuroendocrine systems, In: Loh HH, Roos DH (eds) Neurochemical mechanisms of opiates and endorphins. Raven Press, New York, pp 227–251

    Google Scholar 

  • Houck JC, Kimball C, Chang C, Pedigo NW, Yamamura HI (1980) Placental β-endorphin-like peptides. Science 207:78–80

    Google Scholar 

  • Hughes JT, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR (1975) Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 258:1157–1159

    Google Scholar 

  • Ieiri T, Chen HT, Meites J (1979) Effects of morphine and naloxone on serum levels of luteinizing hormone and prolactin in prepubertal male and female rats. Neuroendocrinology 29:288–292

    Google Scholar 

  • Iwamoto ET, Way EL (1979) Opiate actions and catecholamines. In: Loh HH, Ross DH (eds) Neurochemical mechanisms of opiates and endorphins. New York: Raven Press, pp 357–407

    Google Scholar 

  • Janowsky D, Judd L, Huey L, Roitman N, Parker D (1979) Naloxone effects on serum growth hormone and prolactin in man. Psychopharmacology 65:95–97

    Google Scholar 

  • Kato Y, Iwasaki Y, Abe H, Ohgo S, Imura H (1978) Effects of endorphins on prolactin and growth hormone secretion in rats. Proc Soc Exp Biol Med 158:431–436

    Google Scholar 

  • Kokka N, Garcia JF, George R, Elliott HW (1972) Growth hormone and ACTH secretion: evidence for an inverse relationship in rats. Endocrinology 90:735–743

    Google Scholar 

  • Korf J, Bunney BS, Aghajanian GK (1974) Noradrenergic neurons: morphine inhibition of spontaneous activity. Eur J Pharmacol 25:165–169

    Google Scholar 

  • Lal S, Nair NPV, Cervantes P, Pulman J, Guyda H (1979) Effect of naloxone and levallorphan on serum prolactin concentration and apomorphine-induced growth hormone secretion. Acta Psychiatr Scand 59:173–179

    Google Scholar 

  • Lee S, Paneral AE, Bellarba D, Friesen HG (1980) Effect of endocrine modifications and pharmacological treatments on brain and pituitary concentrations of β-endorphin. Endocrinology 107:245–248

    Google Scholar 

  • Lien EL, Fenichel RL, Garsky V, Sarantakis D, Grant NH (1976) Enkephalin-stimulated prolactin release. Life Sci 19:837–840

    Google Scholar 

  • MacLeod RM (1976) Regulation of prolactin secretion. In: Martini L, Ganong WF (eds) Frontiers in neuroemdocrinology, vol. 4. Raven Press, New York, pp 169–194

    Google Scholar 

  • Martin JB, Audet J, Saunders A (1975) Effects of somatostatin and hypothalamic ventromedial lesions on GH release induced by morphine. Endocrinology 96:839–847

    Google Scholar 

  • Martin JB, Reichlin S, Broen GM (1977) Clinical neuroendocrinology. Davis, Philadelphia

    Google Scholar 

  • Meites J, Bruni JF, Van Vugt DA, Smith AP (1979) Relation of endogenous opioid peptides and morphine to neuroendocrine functions. Life Sci 24:1325–1336

    Google Scholar 

  • Morley JE, Baranetsky NG, Wingert TD, Carlson HE, Hershman JM, Melmed S, Levin SR, Jamison KR, Weitzman R, Chang RJ, Varner AA (1980) Endocrine effects of naloxone-induced opiate receptor blockade. J Clin Endocrinol Metab 50:251–257

    Google Scholar 

  • Pang CN, Zimmermann E, Sawyer CH (1977) Morphine inhibition of the preovulatory surges of plasma luteinizing hormone and follicle stimulating hormone in the rat. Endocrinology 101:1726–1732

    Google Scholar 

  • Persson SA (1979) Effect of morphine on the accumulation of DOPA after decarboxylase inhibition in the rat. Eur J Pharmacol 55:121–128

    Google Scholar 

  • Pert CB, Kuhar MJ, Snyder SH (1975) Autoradiographic localization of the opiate receptor in rat brain. Life Sci 16:1849–1854

    Google Scholar 

  • Pickar D, Davis GC, Schulz C, Extein I, Wagner R, Naber D, Gold PW, van Kammen DP, Goodwin FK, Wyatt RJ, Li CH, Bunney WE, Jr (1981) Behavioral and biological effects of acute β-endorphin injection in schizophrenic and depressed patients. Am J Psychiatry 138:160–166

    Google Scholar 

  • Rossier J, French ED, Rivier C, Guillemin R, Bloom, FE (1977) Foot-shock induced stress increases β-endorphin levels in blood but not brain. Nature 270:618–620

    Google Scholar 

  • Rubin P, Sweezy S, Blaschke T (1979) Naloxone lowers plasma prolactin in man. Lancet II:1293

    Google Scholar 

  • Schulz SC, Wagner R, van Kammen DP, Rogol AD, Davis GC, Wyatt RJ, Pickar D, Bunney WE Jr, Li CH (1980) Prolactin response to β-endorphin in man. Life Sci 27:1735–1741

    Google Scholar 

  • Shaar CJ, Frederickson RCA, Dininger NB, Jackson L (1977) Enkephalin analogues and naloxone modulate the release of growth hormone and prolactin—evidence for regulation by an endogenous opioid peptide in brain. Life Sci 21:853–860

    Google Scholar 

  • Simon EJ (1975) Opiate receptor binding with 3H-etorphine. Opiate receptor mechanisms. Neurosci Res Program Bull 13:43–50

    Google Scholar 

  • Stubbs WA, Jones A, Edwards GRW, Delitalia G, Jeffcoate WJ, Ratter SJ, Besser GM, Bloom SR, Alberti KGM (1978) Hormonal and metabolic response to an enkephalin analogue in normal men. Lancet II:1225–1227

    Google Scholar 

  • Tolis G, Hickey J, Guyda H (1975) Effects of morphine on serum growth hormone, cortisol, prolactin and thyroid stimulating hormone in man. J Endocrinol Metabol 41:797–800

    Google Scholar 

  • Van Loon GR, De Souza EB, Shin SH (1980) Dopaminergic mediation of β-endorphin-induced prolactin secretion. Neuroendocrinology 31:292–296

    Google Scholar 

  • Van Vugt DA, Bruni JF, Sylvester PW, Chen HT, Ieiri T, Meites J (1979) Interaction between opiates and hypothalamic dopamine on prolactin release. Life Sci 24:2361–2368

    Google Scholar 

  • Volavka J, Cho D, Mallya A, Baumann J (1979) Naloxone increases ACTH and cortisol levels in man. N Engl J Med 300:1056–1057

    Google Scholar 

  • Volavka J, Baumann J, Pevnick J, Reke D, James B, Cho D (1980) Shortterm effects of naloxone in man. Psychoneuroendocrinology 5:225–234

    Google Scholar 

  • Von Graffenried B, del Pozo E, Roubizek J, Krebs E, Pöldinger W, Burmeister P, Kerp L (1978) Effects of the synthetic enkephalin analogue FK 33-824 in man. Nature 272:729–730

    Google Scholar 

  • Young WS III, Bird SJ, Kuhar MJ (1977) Iontophoresis of methionineenkephalin in the locus coeruleus area. Brain Res 129:366–370

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Psychiatrische Klinik der Universität München, Federal Republic of Germany

    Dieter Naber

  2. Biological Psychiatry Branch, NIMH, Bethesda, Maryland, USA

    David Pickar, Glenn C. Davis, David C. Jimerson, Emanuel G. Defraites & Monte S. Buchsbaum

  3. Clinical Neuropsychopharmacology Branch, NIMH, Bethesda, Maryland, USA

    Robert M. Cohen, Ned H. Kalin & Samuel C. Risch

  4. Laboratory of Clinical Sciences, NIMH, Bethesda, Maryland, USA

    Mary A. Elchisak

Authors
  1. Dieter Naber
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Pickar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Glenn C. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert M. Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David C. Jimerson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mary A. Elchisak
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Emanuel G. Defraites
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ned H. Kalin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Samuel C. Risch
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Monte S. Buchsbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naber, D., Pickar, D., Davis, G.C. et al. Naloxone effects on β-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers. Psychopharmacology 74, 125–128 (1981). https://doi.org/10.1007/BF00432677

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00432677

Key words

Search

Navigation