Advertisement

Hormonal and Other Effects of Naltrexone in Normal Men

  • J. Volavka
  • A. Mallya
  • J. Bauman
  • J. Pevnick
  • D. Cho
  • D. Reker
  • B. James
  • R. Dornbush
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 116)

Abstract

Many experimental approaches have been devised to study the functions of endorphins. A strategy which has been used very widely consists in the administration of an opiate antagonist. It is assumed that the antagonists displace endorphins from their receptors; once this happens, any function for which endorphins are needed should be altered. It has been hypothesized that endorphins play a role in endocrine functions (see below), pain perception (BUCHSBAUM, DAVIS & BUNNEY, 1977; EL-SOBKY, DOSTROVSKY & WALL, 1976; GREVERT & GOLDSTEIN, 1978; HOSOBUCHI, ADAMS & LINCHITZ, 1977), modulation of mood (JONES, 1978), sexual functioning (GOLDSTEIN & HANSTEEN, 1977), mental health (WATSON et al., 1978; VEREBEY, VOLAVKA & CLOUET, 1978) and other areas. These hypotheses were tested by the administration of the opiate antagonist naloxone. Another opiate antagonist, naltrexone, has also been used for similar experiments: it was administered to rats in order to study the function of endorphins in prolactin release (GUIDOTTI & GRANDISON, 1978); it was also used in therapeutic experiments in psychotic patients (SIMPSON, BRANCHEY & LEE, 1977; GUNNE & TERENIUS, 1978; GITLIN & ROSENBLATT, 1978).

Keywords

Luteinizing Hormone Pain Threshold Sexual Arousal Cortisol Plasma Level Opiate Receptor 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. BLUMBERG, H & DAYTON, H.B. (1972) Narcotic antagonist studies with EN-1639A (N-Cyclopropylmethylnoroxymorphone hydrochloride). In Fifth International Congress on Pharmacology, Volunteer Abstracts. San Francisco, July, p. 23.Google Scholar
  2. BRUNI, J.F., 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.PubMedCrossRefGoogle Scholar
  3. BUCHSBAUM, M.S., DAVIS, G.C. & BUNNEY, W.E. JR. (1977) Naloxone alters pain perception and somatosensory evoked potentials in normal subjects. Nature 270, 620–622.PubMedCrossRefGoogle Scholar
  4. CICERO, T.J., BADGER, T.M., WILCOX, C.E., BELL, R.D. & MEYER, E.R. (1977) Morphine decreases luteinizing hormone by an action on the hypothalamic-pituitary axis. J. Pharmacol. Exp. Ther. 203, 548–555.PubMedGoogle Scholar
  5. CICERO, T.J. & DORNBUSH, R. (1979) in Research Advances in Alcohol and Drug Abuse (Kalant, O., Kalant, H. and Israel, Y., eds.) Vol. 5 (in press). Plenum Press, New York.Google Scholar
  6. EHRLICH, Y.H., BONNET, K.A., DAVIS, L.G. & BRUNNGRABER, E.G. (1978) Decreased phosphorylation of specific proteins in neostriatal membranes from rats after long-term narcotic exposure. Life Sci. 23, 137– 146.PubMedCrossRefGoogle Scholar
  7. EISENMAN, A.J., FRASER, H.F., SLOAN, J. & ISBELL, H. (1958) Urinary 17-Ketosteroid excretion during a cycle of addiction to morphine. J. Pharmacol. Exp. Ther. 124 , 305–311.PubMedGoogle Scholar
  8. EL-SOBKY, A., DOSTROVSKY, J.O. & WALL, P.D. (1976) Lack of effect of naloxone on pain perception in humans. Nature 263, 783–784.PubMedCrossRefGoogle Scholar
  9. FURUYAMA, S., MAYES, D. & NUGENT, C.A. (1970) A radio-immunoassay for plasma testosterone. Steroids 16 , 415.PubMedCrossRefGoogle Scholar
  10. GEORGE, R. & KOKKA, N. (1976) in Tissue Responses to Addictive Drugs (Ford, D.H. and Clouet, D.H., eds.) pp. 527–540. Spectrum, New York.Google Scholar
  11. GITLIN, M. & ROSENBLATT, M. (1978) Possible withdrawal from endogenous opiates in schizophrenics. Am. J. Psychiatry, 135, 377–378.PubMedGoogle Scholar
  12. GOLD, M.S., REDMOND, D.E. JR., DONABEDIAN, R.K. (1978) Prolactin secretion, a measurable central effect of opiate-receptor antagonists. Lancet Feb. 11 , 323–324.CrossRefGoogle Scholar
  13. GOLDSTEIN, A. (1976) Opioid peptides (endorphins) in pituitary and brain. Science 193, 1081–1086.PubMedCrossRefGoogle Scholar
  14. GOLDSTEIN, A. & HANSTEEN, R.W. (1977) Evidence against involvement of endorphins in sexual arousal and orgasm in man. Arch. Gen. Psychiat. 34, 1179–1180.PubMedCrossRefGoogle Scholar
  15. GREVERT, P. & GOLDSTEIN, A. (1978) EndorpHTns: Naloxone fails to alter experimental pain or mood in humans. Science 199, 1093–1095.PubMedCrossRefGoogle Scholar
  16. GUIDOTTI, A. & GRANDISON, L. (1978) in The Endorphins. Advances in Biochemical Pharmacology (Costa, E. and Trabucchi, M., eds.) Vol. 18. Raven Press, New York.Google Scholar
  17. GUILLEMIN, R., VARGO, T., ROSSIER, J., MILNICK, S., LING, N., RIVIER, D., VALE, W., BLOOM, F. (197 7) Beta-endorphin and adrenocorticotropin are secreted con-comitantly by the pituitary gland. Science 197 , 1367–1369.PubMedCrossRefGoogle Scholar
  18. GUNNE, L.M. & TERENIUS, L. (1978) in Endorphins in Mental Health Research (Usdin, E., Bunney, W.E. Jr. and Kline , N.S., eds.). Macmillan Press, New York.Google Scholar
  19. HELLMAN, L., FUKUSHIMA, D.K., ROFFWARG, H. & FISHMAN, J. (1975) Changes in estradiol and cortisol production rates in men under the influence of narcotics. J. Clin. Endocrinol. Metab. 41, 1014–1019.PubMedCrossRefGoogle Scholar
  20. HOSOBUCHI, Y., ADAMS, J.E. & LINCHITZ, R. (1977) Pain relief by electrical stimulation of the central gray matter in humans and its reversal by naloxone. Science 197, 183–186.PubMedCrossRefGoogle Scholar
  21. IRWIN, S., KINOHI, R.G., COLLET, P.M. & BOTTOMLY, D.R. (1974) Acute time-dose-response effects of cyclazocine, naltrexone, and naloxone in man. Proc. Committee on Problems of Drug Dependence. Cambridge , Ma.Google Scholar
  22. JACOBS, L.S., MARIZ, I.K. & DAUGHADAY, W.D. (1972) A mixed heterologous radioimmunoassay for human prolactin. J. Clin. Endocrinol. Metab. 34, 484.PubMedCrossRefGoogle Scholar
  23. JANOWSKY, D., JUDD, L., HUEY, L., ROITMAN, N., PARKER, D. & SEGAL, D. (1978) Negative naloxone effects on serum-prolactin. Lancet Sept. 16, 637.CrossRefGoogle Scholar
  24. JONES, R. (1978) in Endorphins in Mental Health Research (Usdin, E., Bunney, W.E. Jr. and Kline, N.S., eds.). Macmillan Press, New York.Google Scholar
  25. KERLINGER, F.N. & PEDHAZUR, E.J. (1973) Multiple Regression in Behavioral Research. Holt, Rinehart, Winston , New York.Google Scholar
  26. KOKKA, N. & GEORGE, R. (1974) in Narcotics and the Hypothai amus (Zimmerman, E. and George, R., eds.) pp. 137–157. Raven Press, New York.Google Scholar
  27. LAL, H., BROWN, W., DRAWBAUGH, R., HYNES, M., BROWN, G. (1977) Enhanced prolactin inhibition following chronic treatment with haloperidol and morphine. Life Sci. 20 , 101–106.PubMedCrossRefGoogle Scholar
  28. MAINS, R., EIPPER, E. & LING, N. (1977) Common precursor to corticotropins and endorphins. Proc. Natl. Acad. Sci. U.S.A. 74 , 3014.PubMedCrossRefGoogle Scholar
  29. MARTIN, W.R., JASINSKI, D.R. & MANSKY, P.A. (1973) Naltrexone, an antagonist for the treatment of heroin dependence. Arch. Gen. Psychiat. 28, 784–791.PubMedCrossRefGoogle Scholar
  30. MENDELSON, J.H., MEYER, R.E., ELLINGBOE, J., MIRIN, S.M. & MCDOUGLE, M. (197 5) Effects of heroin and methadone on plasma cortisol and testosterone. J. Pharmacol . Exp. Ther. 195, 296–302.PubMedGoogle Scholar
  31. MENDELSON, J.H., ELLINGBOE, J., KEUHNLE, J.C. & MELLO, N.K. Effects of naltrexone on mood and neuroendocrine function in normal adult males. Psychoneuro endocrinology. In press.Google Scholar
  32. NUTT, J.G., ROSIN, A.J., EISLER, T., CALNE, D.B. & CHASE, T.N. (1978) Effect of an opiate antagonist on movement disorders. Arch. Neurol. 35, 810–811.PubMedCrossRefGoogle Scholar
  33. ORTH, D.N. (1974) in Methods of Hormone Radioimmunoassay (McJaffe, B. and Behrman, M.R., eds.). Academic Press, New York.Google Scholar
  34. RIVIER, C., VALE, W., LING, N., BROWN, M. & GUILLEMIN, R. (1977) Stimulation in vivo of the secretion of prolactin and growth hormone by beta-endorphin. Endocrinology 100, 238–241.PubMedCrossRefGoogle Scholar
  35. ROLLERI, E., ZANNINO, M., ORLANDINI, S., & MALVANO, R. (1976) Direct radioimmunoassay of plasma cortisol. Clin. Chim. Acta 66, 319.PubMedCrossRefGoogle Scholar
  36. ROTSZTEJN, W.H., DROUVA, S.V., PATTOU, E. & KORDON, C. (1978) Met-enkephalin inhibits in vitro dopamineinduced LHRH release from mediobasal hypothalamus of male rats. Nature 274, 281–282.PubMedCrossRefGoogle Scholar
  37. SABOL, S.L. (1978) Regulation of endorphin production by glucocorticoids in cultured pituitary tumor cells. Biochem. and Biophys. Res. Comm. 82, 560–567.CrossRefGoogle Scholar
  38. SAXENA, B.B., DERMURA, H., GANDY, H.M. & PETERSON, R.E. (1968) Radioimmunoassay of human follicle-stimulating and luteinizing hormone in plasma. J. Clin. Endocrinol. Metab. 28, 519.PubMedCrossRefGoogle Scholar
  39. SIMPSON, G.M., BRANCHEY, M.H. & LEE, J.H. (1977) A trial of naltrexone in chronic schizophrenia. Curr. Ther. Res. 22, 909–913.Google Scholar
  40. SLOAN, J.W. (1971) in Narcotic Drugs, Biochemical Pharmacology (Clouet, D.H., ed.) pp. 262–282. Plenum Press, New York.Google Scholar
  41. TERENIUS, L. (1976) Somatostatin and ACTH are peptides with partial antagonist-like selectivity for opiate receptors. Eur. J. Pharmacology 38, 211–213.CrossRefGoogle Scholar
  42. VEREBEY, K., VOLAVKA, J. & CLOUET, D. (1978) Endorphins in psychiatry. Arch. Gen. Psychiatry 35, 877–888.PubMedCrossRefGoogle Scholar
  43. VOLAVKA, J., RESNICK, R.B., KESTENBAUM, R.S. & FREEDMAN, A.M. (1976) Short-term effects of naltrexone in 155 heroin ex-addicts. Biological Psychiatry 11, 679–685.PubMedGoogle Scholar
  44. VOLAVKA, J., BAUMAN, J., MALLYA, A. & CHO, D. Effects of naloxone in normal men. In preparation.Google Scholar
  45. WATSON, S.J., BERGER, P.A., AKIL, H. MILLS, M.J. & BARCHAS, J.D. (1978) Effects of naloxone on schizophrenia: reduction in hallucinations in a subpopulation of subjects. Science 201, 73–76.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • J. Volavka
    • 1
  • A. Mallya
    • 1
  • J. Bauman
    • 2
  • J. Pevnick
    • 1
  • D. Cho
    • 1
  • D. Reker
    • 1
  • B. James
    • 1
  • R. Dornbush
    • 3
  1. 1.Missouri Institute of PsychiatryUniversity of Missouri Columbia-School of MedicineSt. LouisUSA
  2. 2.Masters and Johnson InstituteSt. LouisUSA
  3. 3.New York Medical CollegeValhallaUSA

Personalised recommendations