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Opioid receptors: Some perspectives from early studies of their role in normal physiology, stress responsivity, and in specific addictive diseases

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Abstract

The early history of research on the possible existence of specific opioid receptors and on developing a new form of pharmacotherapy for the treatment of heroin addiction in New York City, from 1960–1973, along with the special relationships between two leading scientists conducting these research efforts, Dr. Eric Simon and Dr. Vincent P. Dole Jr., are presented in a historical perspective. The linkage of these early efforts and the subsequent identification and the elucidation of the effects of exogenous opiates acting at specific opiate receptors in human physiology, including some findings from perspective studies of heroin addicts at time of entry to and during methadone maintenance treatment, are presented in the context of the important clues which thereby were provided concerning the possible roles of the endogenous opioids in normal mammalian physiology. From many of these early clinical research findings and studies in animal models, the hypothesis that the endogenous opioids system may play an important role in stress responsivity was formulated along with the related hypothesis, first presented in the early 1970s, that an atypical responsivity to stress and stressors might be involved in the acquisition and persistence of, and relapse to specific addictive diseases, including heroin addiction, cocaine dependency and alcoholism. More recent studies of the possible involvement of the specific opioid receptors in these three addictive diseases—heroin addiction, cocaine addiction and alcoholism—from our laboratory are discussed in a historical perspective of the development of these ideas from the early research findings of not only Dr. Eric Simon, but his numerous colleagues in opioid research in the United States and throughout the world.

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References

  1. Simon, E. J. 1963. Inhibition of RNA synthesis of E. Coli by the narcotic drug levorphanol. Nature. 198:794.

    Article  PubMed  CAS  Google Scholar 

  2. Simon, E. J. 1964. Inhibition of bacterial growth by drugs of the morphine series. Science. 144:543.

    Article  PubMed  CAS  Google Scholar 

  3. Simon, E. J. and Van Praag, D. 1964. The inhibition of RNA synthesis in E. Coli by levorphanol. Proc. Natl. Acad. Sci. USA. 51:877.

    Article  PubMed  CAS  Google Scholar 

  4. Simon, E. J. and Van Praag, D. 1964. Selective inhibition of ribosomal RNA synthesis in E. Coli by levorphanol. Proc. Natl. Acad. Sci. USA. 51:1151.

    Article  PubMed  CAS  Google Scholar 

  5. Dole, V. P., Nyswander, M. E. and Kreek, M. J.: Narcotic blockade. Arch. Intern. Med., 118:304–309, 1966.

    Article  PubMed  CAS  Google Scholar 

  6. Kreek, M. J. 1992. Epilogue: Medical maintenance treatment for heroin addiction, from a retrospective and prospective viewpoint. Pages 255–272,in State Methadone Maintenance Treatment Guidelines. Office for Treatment Improvement, Division for State Assistance.

  7. Kreek, M. J. 1992. The addict as a patient. Pages 997–1009,in Lowinson, J. H., Ruiz, P., Millman, R. B., and Langrod, J. G., (eds.), Substance Abuse: A Comprehensive Textbook. Williams & Wilkins, Baltimore, Maryland.

    Google Scholar 

  8. Nyswander, M. 1956. The drug addict as a patient. Grune & Stratton, New York.

    Google Scholar 

  9. Dole, V. P., Nyswander, M. E. and Kreek, M. J.: Narcotic blockade: a medical technique for stopping heroin use by addicts. Trans. Assoc. Am. Phys. 79:122–136, 1966.

    PubMed  CAS  Google Scholar 

  10. Kreek, M. J. 1991. Using methadone effectively: Achieving goals by application of laboratory, clinical, and evaluation research and by development of innovative programs. Pages 245–266,in Pickens, R., Leukefeld, C., and Schuster, C. R. (eds.) Improving Drug Abuse Treatment, NIDA Research Monograph Series 106, Rockville, MD.

  11. Kreek, M. J. 1992. Rationale for maintenance pharmacotherapy of opiate dependence. Pages 205–230,in O'Brien, C. P. and Jaffe, J. H. (eds.), Addictive States, Raven Press, Ltd., New York.

    Google Scholar 

  12. Kreek, M. J. 1996. Long-term pharmacotherapy for opiate (primarily heroin) addiction: Opiate Agonists. Pages 487–541,in Schuster, C. R. and Kuhar, M. J. (eds.), Pharmacological Aspects of Drug Dependence: Toward an Integrated Neurobehavioral Approach, Springer-Verlag, Berlin.

    Chapter  Google Scholar 

  13. Kreek, M. J. 1996. Opiates, opioids and addiction. Mol. Psych., in press.

  14. Kreek, M. J. 1996. Cocaine, dopamine and the endogenous opioid system. Journal of Addictive Diseases, (in press).

  15. McLellan, A. T., Arndt, I. O., Metzger, D. S., Woody, G. E., and O'Brien, C. P. 1993. The effects of psychosocial services in substance abuse treatment. JAMA 269(15):1953–1959.

    Article  PubMed  CAS  Google Scholar 

  16. Ball, J. C. and Ross, A. 1991. The effectiveness of methadone maintenance treatment: Patients, programs, services, and outcome. Springer-Verlag, New York.

    Book  Google Scholar 

  17. Inturrisi, C. E. and Verebely, K. 1972. The levels of methadone in the plasma in methadone maintenance. Clin. Pharm. and Ther., 18:633–637.

    Google Scholar 

  18. Inturrisi, C. E. and Verebely, K. 1972. Disposition of methadone in man after a single oral dose. Clin. Pharmacol. Ther., 13:923–930.

    PubMed  CAS  Google Scholar 

  19. Dole, V. P. and Kreek, M. J. 1973. Methadone plasma level: Sustained by a reservoir of drug in tissue. Proc. Natl. Acad. Sci., 70:10.

    Article  PubMed  CAS  Google Scholar 

  20. Kreek, M. J. 1973. Plasma and urine levels of methadone. N.Y. State J. Med., 73:2773–2777.

    PubMed  CAS  Google Scholar 

  21. Kreek, M. J., Garfield, J. W., Gutjahr, C. L. and Giusti, L. M. 1976. Rifampin-induced methadone withdrawal. New Engl. J. Med., 294:1104–1106.

    Article  PubMed  CAS  Google Scholar 

  22. Kreek, M. J., Gutjahr, C. L., Garfield, J. W., Bowen, D. V., and Field, F. H. 1976. Drug interactions with methadone. Ann. N.Y. Acad. Sci., 281:350–370.

    Article  PubMed  CAS  Google Scholar 

  23. Hachey, D. L., Kreek, M. J. and Mattson, D. H. 1977. Quantitative analysis of methadone in biological fluids using deuteriumlabeled methadone and GLC-chemical-ionization mass spectrometry. J. Pharm. Sci., 66:1579–1582.

    Article  PubMed  CAS  Google Scholar 

  24. Rubenstein, R. B., Kreek, M. J., Mbawa, N., Wolff, W. I., Korn, R., and Gutjahr, C. L. 1978. Human spinal fluid methadone levels. Drug and Alc. Dep., 3:103–106.

    Article  CAS  Google Scholar 

  25. Kreek, M. J., Hachey, D. L. and Klein, P. D. 1979. Stereoselective disposition of methadone in man. Life Sci., 24:925–932.

    Article  PubMed  CAS  Google Scholar 

  26. Kreek, M. J., Bencsath, F. A. and Field, F. H. 1980. Effects of liver disease on urinary excretion of methadone and metabolites in maintenance patients: Quantitation by direct probe chemical ionization mass spectrometry. Biomedical Mass Spectrometry, 7: 385–395.

    Article  PubMed  CAS  Google Scholar 

  27. Novick, D. M., Kreek, M. J., Fanizza, A. M., Yancovitz, S. R., Gelb, A. M. and Stenger, R. J. 1981. Methadone disposition in patients with chronic liver disease. Clin. Pharmacol. Ther., 30: 353–362.

    Article  PubMed  CAS  Google Scholar 

  28. Nakamura, K., Hachey, D. L., Kreek, M. J., Irving, C. S., and Klein, P. D. 1982. Quantitation of methadone enantiomers in humans using stable isotope-labeled2H5,2H8 methadone. J. Pharm. Sci. 71:39–43.

    Google Scholar 

  29. Kreek, M. J., Bencsath, F. A., Fanizza, A. and Field, F. H. 1983. Effects of liver disease on fecal excretion of methadone and its unconjugated metabolites in maintenance patients: Quantitation by direct probe chemical ionization mass spectrometry. Biomed. Mass. Spectrm. 10:544–549.

    Article  CAS  Google Scholar 

  30. Ingoglia, N. A. and Dole, V. P. 1970. Localization of d- and 1-methadone after intra ventricular injection into rat brain. J. Pet. and Ther. 175:84–87.

    CAS  Google Scholar 

  31. Dole, V. P. 1970. Biochemistry of Addiction. Ann. Rev. of Biochem. 39:821–840.

    Article  CAS  Google Scholar 

  32. Harte, E. H., Gutjahr, C. L., and Kreek, M. J. 1976. Long-term persistence of dl-methadone in tissues. Clin. Res. 24:623A.

    Google Scholar 

  33. Goldstein, A., Lowney, L. T., and Pal, B. K. 1971. Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain. Proc. Nat. Acad. Sci. USA. 68:1742–1747.

    Article  PubMed  CAS  Google Scholar 

  34. Pert, C. B., and Snyder, S. H. 1973. Opiate receptor: demonstration in nervous tissue. Science 179:1011–1014.

    Article  PubMed  CAS  Google Scholar 

  35. Simon, E. J., Hiller, J. M., and Edelman, I. 1973. Stereospecific binding of the potent narcotic analgesic [3H]Etorphine to ratbrain homogenate. Proceedings of the National Academy of Sciences. 70:1947–1949.

    Article  CAS  Google Scholar 

  36. Terenius, L. 1973. Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex. Acta Pharmacologica ET Toxicologica. 32:317–320.

    Article  PubMed  CAS  Google Scholar 

  37. Dole, V. P., and Nyswander, M. E. 1965. A medical treatment for diacetylmorphine (heroin) addiction. JAMA. 193:646–650.

    Article  PubMed  CAS  Google Scholar 

  38. Kreek, M. J. 1972. Medical safety, side effects and toxicity of methadone. Proceedings of the Fourth National Conference on Methadone Treatment, NAPAN-NIMH, 171–174.

  39. Kreek, M. J., Dodes, L., Kane, S, Knobler, J. and Martin, R. 1972. Long-term methadone maintenance therapy: Effects on liver function. Ann. Intern. Med., 77:598–602.

    PubMed  CAS  Google Scholar 

  40. Kreek, M. J. 1973. Medical safety and side effects of methadone in tolerant individuals. J. Amer. Med. Assn., 223:665–668.

    Article  CAS  Google Scholar 

  41. Kreek, M. J. 1973. Physiological implications of methadone treatment.in Methadone Treatment Manual, U.S. Dept. of Justice (USGPO) 2700-00227, Washington, D.C. 85–91.

  42. Cushman, P., and Kreek, M. J. 1974. Methadone-maintained patients. Effects of methadone on plasma testosterone, FSH, LH and prolactin. N.Y. State J. Med. 74:1970–1973.

    PubMed  Google Scholar 

  43. Kreek, M. J. 1978. Medical complications in methadone patients. Ann. N.Y. Acad. Sci., 311:110–134.

    Article  PubMed  CAS  Google Scholar 

  44. Cushman, P., and Kreek, M. J. 1974. Some endocrinologic observations in narcotic addicts. Pages 161–173,in Zimmerman, E. and George, R. (eds.), Narcotic and the Hypothalamus, Raven Press, New York, NY.

    Google Scholar 

  45. Novick, D. M., Ochshorn, M., Ghali, V., Croxson, T. S., Mercer, W. D., Chiorazzi, N., and Kreek, M. J. 1989. Natural killer cell activity and lymphocyte subsets in parenteral heroin abusers and long-term methadone maintenance patients. J. Pharm. Exper. Ther. 250:606–610.

    CAS  Google Scholar 

  46. Culpepper-Morgan, J. A., Inturrisi, C. E., Portenoy, R. K., Foley, K., Houde, R. W., Marsh, F., and Kreek, M. J. 1992. Treatment of opioid induced constipation with oral naloxone: A pilot study. Clin. Pharm. Ther. 23:90–95.

    Google Scholar 

  47. Novick, D. M., Richman, B. L., Friedman, J. M., Friedman, J. E., Fried, C., Wilson, J. P., Townley, A., and Kreek, M. J. 1993. The medical status of methadone maintained patients in treatment for 11–18 years. Drug and Alc. Dep. 33:235–245.

    Article  CAS  Google Scholar 

  48. Kreek, M. J., Schaefer, R. A., Hahn, E. F. and Fishman, J. 1983. Naloxone, a specific opioid antagonist, reverses chronic idiopathic constipation. Lancet, Feb. 5, 261–262.

    Article  Google Scholar 

  49. Kreek, M. J., Fishman, J., Hahn, E. F., and Schaefer, R. A. 1983. Naloxone in chronic constipation (Letter to the editor). Lancet, April 2, 758.

  50. Culpepper-Morgan, J., Kreek, M. J., Holt, P. R., La Roche, D., Zhang, J., and O'Bryan, L. 1988. Orally administered kappa as well as mu opiate delay gastrointestinal transit time in the guinea pig. Life Sciences, 42:2073–2077.

    Article  PubMed  CAS  Google Scholar 

  51. Culpepper-Morgan, J. A., Holt, P. R., LaRoche, D., and Kreek, M. J. 1995. Orally administered opioid antagonists reverse both mu and kappa opioid agonist delay of gastrointestinal transit in the guinea pig. Life Sciences. 56:1187–1192.

    Article  PubMed  CAS  Google Scholar 

  52. Kreek, M. J. and Culpepper-Morgan, J. A. 1994. Constipation syndromes. Pages 179–208,in Lewis, J. H. (ed.) A Pharmacologic Approach to Gastrointestinal Disorders.

  53. Zhang, J. S., Plevy, S., Albeck, H., Culpepper-Morgan, J., Friedman, J. and Kreek, M. J.: Effects of age on distribution of preproenkephalin-like mRNA in the gastrointestinal tract of the guinea pig. Advances in the Biosciences: Proceedings of 1988 INRC meeting, 75:349–350, 1989.

    CAS  Google Scholar 

  54. Zhang, J., Albeck, H., Culpepper-Morgan, J., Friedman, J., and Kreek, M. J. 1988. Distribution of preproenkephalin mRNA in the gastrointestinal tract of the guinea pig. Clinical Research, 36: 402A.

    Google Scholar 

  55. Yuferov, V. P., LaForge, K. S., Spangler, R., Maggos, C. E., and Kreek, M. J. 1996. Guinea Pig Preprodynorphin mRNA: Primary structure and regional quantitation in the brain. DNA and Cell Biology, (in press).

  56. Yuferov, V., Culpepper-Morgan, J. A., Claye, L. H., LaForge, K. S., and Kreek, M. J. 1995. Quantification of preprodynorphin (DYN) mRNA in guinea pig gut using a highly sensitive solution hybridization assay. Abstracts of the AGA Meeting, Digestive Disease Week.

  57. Eisenman, A. J., Fraser, H. F., Sloan, J., and Isbell H. 1958. Urinary 17-ketosteroid excretion during a cycle of addiction to morphine. JPET 124:305–311.

    CAS  Google Scholar 

  58. Stimmel, B., and Kreek, M. J. 1975. Pharmacologic actions of heroin.in: B. Stimmel, (ed.) Heroin dependency: Medical, economic and social aspects, New York, NY: Stratton Intercontinental Medical Book Corp., 71–87.

    Google Scholar 

  59. Kreek, M. J. 1975. Pharmacologic modalities of therapy: Methadone maintenance and the use of narcotic antagonists. in B. Stimmel, (ed), Heroin dependency: Medical, economic and social aspects, New York, NY: Stratton Intercontinental Medical Book Corp., 232–290.

    Google Scholar 

  60. Kreek, M. J., Wardlaw, S. L., Friedman, J., Schneider, B., and Frantz, A. G. 1981. Effects of chronic exogenous opioid administration on levels of one endogenous opioid (beta-endorphin) in man. Pages 364–366in Simon, E. and Takagi, H. (eds.) Advances in Endogenous and Exogenous Opioids,: Kodansha Ltd. Publishers, Tokyo, Japan.

    Google Scholar 

  61. Kreek, M. J., and Hartman, N. 1982. Chronic use of opioids and antipsychotic drugs: Side effects, effects on endogenous opioids and toxicity. Ann. N.Y. Acad. Sci., 398:151–172.

    Article  PubMed  CAS  Google Scholar 

  62. Kreek, M. J., Wardlaw, S. L., Hartman, N. Raghunath, J., Friedman, J., Schneider, B., and Frantz, A. G. 1983. Circadian rhythms and levels of beta-endorphin, ACTH, and cortisol during chronic methadone maintenance treatment in humans. Life Sciences, Sup. I. 33:409–411.

    Article  CAS  Google Scholar 

  63. Kreek, M. J., Raghunath, J., Plevy, S., Hamer, D., Schneider, B., and Hartman, N. 1984. ACTH, cortisol and beta-endorphin response to metyrapone testing during chronic methadone maintenance treatment in humans. Neuropeptides. 5:277–278.

    Article  PubMed  CAS  Google Scholar 

  64. Kennedy, J. A., Hartman, N., Sbriglio, R., Khuri, E., and Kreek, M. J. 1990. Metyrapone-induced withdrawal symptoms. Brit. J. Addict. 85:1133–1140.

    Article  CAS  Google Scholar 

  65. Piazza, P. V., Maccrii, S., Deminiere, J.-M., Le Moal, M., Mormede, M., and Simon, H. 1991. Corticosterone levels determine individual vulnerability to amphetamine self-administration. Proc. Natl. Acad. Sci. USA. 33:2088–2092.

    Article  Google Scholar 

  66. Piazza, P. V., Deroche, V., Deminiere, J.-M., Maccari, S., Le Moal, M., and Simon, H. 1993. Corticosterone in the range of stress-induced levels possesses reinforcing properties: Implication for sensation-seeking behaviors. Proc. Natl. Acad. Sci. USA. 90:11738–11742.

    Article  PubMed  CAS  Google Scholar 

  67. Piazza, P. V., Deminiere, J-M., Le Moal, M., and Simon, H. 1994. Factors that predict individual vulnerability to amphetamine self-administration. Science. 245:1511–1514.

    Article  Google Scholar 

  68. Piazza, P. V., Marinelli, M., Jodogone, C., Deroche, V., Rouge-Pont, F., Maccari, S., Le Moal, M., and Simon, H. 1994. Inhibition of corticosterone synthesis by metyrapone decreases cocainc-induced locomotion and relapse of cocaine self-administration. Brain Res. 658:259–264.

    Article  PubMed  CAS  Google Scholar 

  69. Kreek, M. J. 1987. Multiple drug abuse patterns and medical consequences. Pages 1597–1604,in Meltzer, H. Y., (ed.) Psychopharmacology: The Third Generation of Progress, Raven Press, New York.

    Google Scholar 

  70. Kreek, M. J. 1992. Rationale for maintenance pharmacotherapy of opiate dependence. Pages 205–230,in O'Brien, C. P. and Jaffe, J. H. (eds.), Addictive States. Raven Press, Ltd., New York.

    Google Scholar 

  71. Kreek, M. J., Bencsath, F. A., and Field, F. H. 1980. Effects of liver disease on urinary excretion of methadone and metabolites in maintenance patients: Quantitation by direct probe chemical ionization mass spectrometry. Biomedical Mass Spectrometry. 7: 385–395.

    Article  PubMed  CAS  Google Scholar 

  72. Kreek, M. J. 1988. Cocaine effects on neuroendocrine function: relationships to opiate effects and implications for immunological function. Abstracts of the American College of Neuropsychopharmacology.

  73. Kreek, M. J., Raghunath, J., Spagnoli, D., Mueller, D., Stubbs, V., and Paris, P. 1986. Possible age-related changes in levels of beta-endorphin in humans. Alcohol Drug Res. 6:117.

    Google Scholar 

  74. Kreek, M. J., Marsh, F., Albeck, H., Kutscher, J., Schmugler, J., Connor, B., and Schaefer, R. A. 1986. Effects of opioid antagonist naloxone on fecal evacuation in patients with idiopathic chronic constipation, irritable bowel syndrome, and narcotic-induced constipation. Alcohol Drug Res. 6:168.

    Google Scholar 

  75. Kreek, M. J., Paris, P. Beber, C., Bartol, M. A., Newton, B., Mueller, D., Ferdinands, L., and Spagnoli, D. 1986. Improvement of fecal evacuation in geriatric patients by oral administration of the specific opioid antagonist naloxone. Abstracts of the Clinical Pharmacological and Therapeutic Meeting, Stockholm, Sweden.

  76. Culpepper-Morgan, J. A., Holt, P. R., and Kreek, M. J. 1988. Colonic opiate receptors change with age: Preliminary data. Page 267,in Harris, L. S. (ed.) Problems of Drug Dependence, 1987; Proceedings of the 49th Annual Scientific Meeting of the Committee on Problems of Drug Dependence, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub.s No. (ADM)88-1564, National Institute of Drug Research Monography Series, Washington, D.C.

  77. Hahn, E. F., Lahita, R., Kreek, M. J., Duma, C., and Inturrisi, C. E. 1983. Noloxone radioimmunoassay: An improved antiserum. J. Pharm. Pharmacol. 35:833–836.

    Article  PubMed  CAS  Google Scholar 

  78. Albeck, H., Woodfield, S., and Kreek, M. J. 1989. Quantitative and pharmacokinetic analysis of naloxone in plasma using high performance liquid chromatography with electrochemical detection and solid phase extraction. J. Chromatog. 488:435–445.

    Article  CAS  Google Scholar 

  79. Kreek, M. J., Schneider, B. S., Raghunath, J., and Plevy, S. 1984. Prolonged (24 hour) infusion of the opioid antagonist naloxone does not significantly alter plasma levels of cortisol and ACTH in humans. Abstracts of the Seventh International Congress of Endocrinology, Excerpta, Medica, International Congress Series 652, Amsterdam Oxford-Princeton: 845.

  80. Volavka, J., Bauman, J., Pevnick, J., Reker, D., James, B., and Cho, D. 1980. Short-term hormonal effects of naloxone in man. Psychoneuroend. 5:225–234.

    Article  CAS  Google Scholar 

  81. Kreek, M. J., Ochshorn, M., Ferdinands, L., O'Bryan, L., Carty, A. 1987. Hypothalamic-pituitary-adrenal axis (HPA) effects in humans of a new opioid antagonist nalmefene with mu and kappa receptor subtype activity. Abstracts of the 1987 INRC Conference. Adelaide, Australia.

  82. Schluger, J., Porter, M., Maniar, N., Gunduz, M., Ho, A., and Kreek, M. J. 1996. Differential effects of two opioid antagonists on hypothalamic pituitary adrenal (HPA) axis function in normal controls,in Harris L. (ed.) Abstracts for the College on Problems of Drug Dependence, 58th Annual Scientific Meeting of the College on Problems of Drug Dependence, in press.

  83. Chou, J. Z., Albeck, H., and Kreek, M. J. 1993. Determination of nalmefene in plasma by high performance liquid chromatography with electrochemical detection and its application in pharmacokinetic studies. J. Chromatog. 613:359–364.

    Article  CAS  Google Scholar 

  84. Rosen, M. I., McMahon, T. J., Margolin, A, Gill, T. S., Woods, S. W., Pearsall, H. R., Kreek, M. J., and Kosten, T. R. 1995. Reliability of sequential naloxone challenge tests. Amer. J. Drug. Alc. Abuse. 4:453–467.

    Article  Google Scholar 

  85. Rosen, M. I., McMahon, T. J., Hameedi, F. A., Pearsall, H. R., Woods, S. W., Kreek, M. J., and Kosten, T. R. 1996. Effect of clonidine pretreatment on naloxone-precipitate opiate withdrawal. J. Pharmacol. and Exp. Therapeutics. 276:1128–1135.

    CAS  Google Scholar 

  86. Kosten, T. R., Kreek, M. J., Raghunath, J., and Kleber, H. D. 1986. Cortisol levels during chronic naltrexone maintenance treatment in ex-opiate addicts. Biological Psychiatry. 21:217–220.

    Article  PubMed  CAS  Google Scholar 

  87. Kosten, T. R., Kreek, M. J., Raglunath, J., and Kleber, H. D. 1986. A preliminary study of beta-endorphin during chronic naltrexone maintenance treatment in exp-opiate addicts. Life Sciences, 39:55–59.

    Article  PubMed  CAS  Google Scholar 

  88. Kosten, T. R., Morgan, C., and Kreek, M. J. 1992. Beta-endorphin levels during heroin, methadone, buprenorphine and naloxone challenges: Preliminary findings. Biolog. Psych. 32:523–528.

    Article  CAS  Google Scholar 

  89. Young, E. A., and Akil, H. 1985. Corticotropin-releasing factor stimulation of adrenocorticotropin and beta-endorphin release: Effects of acute and chronic stress. Endocrinology. 117:23–30.

    Article  PubMed  CAS  Google Scholar 

  90. Culpepper-Morgan, J. M., Twist, D. J., Petrillo, C. R., Soda, K. M. and Kreek, M. J. 1992. Beta-endorphin and cortisol abnormalities in spinal cord injured individuals. Metabolism. 41:578–581.

    Article  PubMed  CAS  Google Scholar 

  91. Twist, D. J., Culpepper-Morgan, J. A., Ragnarsson, K. T., Petrillo, C. R., and Kreek, M. J. 1992. Neuroendocrine changes during functional electrical stimulation. Am. J. Phys. Med. & Rehab. 71:156–163.

    Article  CAS  Google Scholar 

  92. Zhou, Y., Spangler, R., LaForge, K. S., Maggos, C. E., Kreek, M. J. 1996. Modulation of CRF-R1 mRNA in rat anterior pituitary by dexamethaxone: correlation with POMC mRNA. Peptides. in press.

  93. Zhou, Y.; Spangler, R.; LaForge, K. S.; Maggos, C. E., Ho, A. and Kreek, M. J. 1996. Corticotropin-releasing factor and CRF-R1 mRNAs in rat brain and pituitary during “binge” pattern cocaine administration and chronic withdrawal. JPET, in press.

  94. Kreek, M. J. and Culpepper-Morgan, J. 1991. Neuroendocrine (HPA) and gastrointestinal effects of opiate antagonists: Possible therapeutic application. Page 168–174,in Harris, L. S., (ed.), Problems of Drug Dependence, 1990: Proceedings of the 52nd Annual Scientific Meeting of the Committee on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series. Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (ADM) 91-1753, Washington, D.C.

  95. Unterwald, E. M., Rubenfeld, J. M., Imai, Y., Wang, J.-B., Uhl, G. R., and Kreek, M. J. 1995. Chronic opioid antagonist administration upregulates mu opioid receptor binding without altering mu opioid receptor mRNA levels. Mol. Brain Res. 33:351–355.

    Article  PubMed  CAS  Google Scholar 

  96. Kreek, M. J. 1992. Methadone disposition during the perinatal period in humans.Pharmac. Biochem. Behav. 11, Suppl.:1–7.

    Google Scholar 

  97. Burstein, Y., Grady, R. W., Kreek, M. J., Rausen, A. R., and Peterson, C. M. 1980. Thrombocytosis in the offspring of female mice receiving dl-methadone. Proc. Soc. Exp. Biol. Med. 164: 275–279.

    PubMed  CAS  Google Scholar 

  98. Unterwald, E., Rubenfeld, J. M., Kreuter, J., Kreek, M. J. 1996. Mu opioid receptor mRNA levels following chronic administration of opioid ligands. Analgesia, in press.

  99. Kling, M., Borg, L., Zametkin, A., Schluger, J., Carson, R., Matochik, J., Maslansky, R., Khuri, E., Wells, A., Lampert, S., Lefter, L., Kreek, M. J. 1996. Opioid receptor binding in methadone maintained former heroin addicts by PET imaging using (18F)cyclofoxy.in Harris, L. (ed.) Problems of Drug Dependence, 1996; Proceedings of the 58th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, in press.

  100. Maggos, C. E., Spangler, R., Perl, D. P., Morgello, S., Simonin, F., Keiffer, B. L., Yuferov, V. and Kreek, M. J. 1996. Human kappa opioid receptor mRNA levels: Quantitation using solution hybridization followed by TCA precipitation.in Harris, L. (ed.) Problems of Drug Dependence, 1996; Proceedings of the 58th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, in press.

  101. Volpicelli, J. R., Alterman, A. I., Hayashida, M., and O'Brien, C. P. 1992. Naltrexone in the treatment of alcohol dependence. Arch. Gen. Psychiatry, 49:876–880.

    Article  PubMed  CAS  Google Scholar 

  102. Volpicelli, J. R., Watson, N. T., King, A. C., Sherman, C. E., and O'Brien, C. P. 1995. Eflect of naltrexone on alcohol “high” in alcoholics. Amer. J. of Psych. 152:613–15.

    CAS  Google Scholar 

  103. O'Malley, S. S., Jaffe, A. J., Change, G., Schottenfeld, R. S., Meyer, R. E., and Rounsaville, B. J. 1992. Naltrexone and coping skills therapy for alcohol dependence. Arch. Gen. Psychiatry. 49: 881–887.

    Article  PubMed  Google Scholar 

  104. Mason, B. J., Ritvo, E. C., Morgan, R. O., Salvato, F. R., Goldberg, G., Welch, B., and Mantero-Atienza, E. 1994. A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence. Alcohol Clin. Exp. Res. 18:1162–1167.

    Article  PubMed  CAS  Google Scholar 

  105. King, A. C., Volpicelli, J. R., Gunduz, M., O'Brien, C. P., and Kreek, M. J. 1996. Naltrexone biotransformation and subjective response to alcohol in social drinkers. Alcoholism: Clin. Expt. Res. 20:44A.

    Google Scholar 

  106. Kreek, M. J. 1981. Metabolic interactions between opiates and alcohol. Ann. N.Y. Acad. Sci. 362:36–49.

    Article  PubMed  CAS  Google Scholar 

  107. Ragavan, V. V., Wardlaw, S. L., Kreek, M. J., and Frantz, A. G. 1983. Effect of chronic naltrexone and methadone administration on brain immunoreactive beta-endorphin in the rat. Neuroendocrinology. 37:266–268.

    Article  PubMed  CAS  Google Scholar 

  108. Kosten, T. R., Kreek, M. J., Swift, C., Carney, M. K., and Ferdinands, L. 1987. Beta-endorphin levels in CSF during methadone maintenance. Life Sciences. 41:1071–1076.

    Article  PubMed  CAS  Google Scholar 

  109. Kreek, M. J. 1987. Tolerance and dependence: Implications for the pharmacological treatment of addiction. Pages 53–61,in Harris, L. S., (ed.), Problems of Drug Dependence, 1986; Proceedings of the 48th Annual Scientific Meeting of The Committee on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (ADM) 87-1508, Washington, D.C.

  110. Kreek, M. J. 1988. Opiate-ethanol interactions: Implications for the biological basis and treatment of combined addictive diseases. Pages 428–239,in Harris, L. S. (ed.), Problems of Drug Dependence, 1987; Proceedings of the 49th Annual Scientific Meeting of the Committee on Problems of Drug Dependence. National Insitute of Drug Abuse Research Monograph Series, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (ADM)88-1564. Washington, D.C.

  111. Branch, A. D., Unterwald, E. M., Lee, S. E., and Kreek, M. J. 1992. Quantitation of preproenkephalin mRNA levels in brain regions from male Fischer rats following chronic cocaine treatment using a recently developed solution hybridization procedure. Mol. Brain. Res. 14:231–238.

    Article  PubMed  CAS  Google Scholar 

  112. Unterwald, E. M., Horne-King, J., and Kreek, M. J. 1992. Chronic cocaine alters brain mu opioid receptors. Brain Res. 584: 314–318.

    Article  PubMed  CAS  Google Scholar 

  113. Spangler, R., Unterwald, E. M., Branch, A., Ho, A., and Kreek, M. J. 1993. Chronic cocaine administration increases prodynorphin mRNA levels in the caudate putamen of rats. Page 142in Harris, L. S. (ed.), Problems of Drug Dependence, 1992; Proceedings of the 54th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (AD1994. Study of dynorphin A (1–17)in vivo processing in rat by microdialysis and matrix-assisted M) 93-3505, Washington, D.C.

  114. Maisonneuve, I. M., Albeck, H., and Kreek, M. J. 1993. Effects of a series of acute cocaine injections on the dopaminergic systems in rats: Anin vivo microdialysis study. Page 396,in Harris, L. S. (ed.), Problems of Drug Dependence, 1992; Proceedings of the 54th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monography Series, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (ADM) 93-3505, Washington, D.C.

  115. Unterwald, E. M., Cox, B. M., Kreek, M. J., Cote, T. E., and Izenwasser, S. 1993. Chronic repeated cocaine adminstration alters basal and opioid-regulated adenylyl cyclase activity. Synapse. 15:33–38.

    Article  PubMed  CAS  Google Scholar 

  116. Spangler, R., Unterwald, E. M., and Kreek, M. J. 1993. ‘Binge’ cocaine administration induces a sustained increase of prodynorphine mRNA in rat caudate-putamen. Mol. Brain. Res. 19:323–327.

    Article  PubMed  CAS  Google Scholar 

  117. Chou, J. Z., Maisonneuve, I. M., Chait, B. T., and Kreek, M. J. 1994. Study of dynorphin A(1–17)in vivo processing in rat brain by microdialysis and matrix-assisted laser desorption mass spectrometry. Page 240,in Harris, L. S. (ed.), Problems of Drug Dependence, 1993; Proceedings of the 55th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (ADM)94-3749, Washingnton, D.C.

  118. Maisonneuve, I. M., and Kreek, M. J. 1994. Acute tolerance to the dopamine response induced by a binge pattern of cocaine administration in male rats: Anin vivo microdialysis study. J. Pharmacol. and Exp. Therapeutics. 268(2):916–921.

    CAS  Google Scholar 

  119. Unterwald, E. M., Rubenfeld, J. M., and Kreek, M. J. 1994. Repeated cocaine administration upregulates κ and μ, but not δ, opioid receptors. NeuroReport. 5:1613–1616.

    Article  PubMed  CAS  Google Scholar 

  120. Unterwald, E. M., Ho, A., Rubenfeld, J. M., and Kreek, M. J. 1994. Time course of the development of behavioral sensitization and dopamine receptor upregulation during binge cocaine administration. J. Pharmacol. and Exp. Therapeutics 270(3):1387–1397.

    CAS  Google Scholar 

  121. Maisonneuve, I. M., Ho, A., and Kreek, M. J. 1995. Chronic administration of a cocaine “binge” alters basal extracellular levels in male rats: Anin vivo microdialysis study. J. Pharmacol. and Exp. Therapeutics 272:652–657.

    CAS  Google Scholar 

  122. Spangler, R., Ho, A., Zhou, Y., Maggos, C., Yuferov, V., Kreek, M. J. 1996. Regulation of kappa opioid receptor mRNA in the rat brain by “binge” pattern cocaine administration and correlation with preprodynorphin mRNA. Mol. Brain Res. 38:71–76.

    Article  PubMed  CAS  Google Scholar 

  123. Spangler, R., Zhou, Y., Maggos, C. E., Zlobin, A., Ho, A., and Kreek, M. J. Dopamine antagonist and q “binge” cocaine effects on rat opioid and dopamine transporter mRNAs.Neuroreport, in press.

  124. Zubieta, J-K,in Harris, L. (ed.) Problems of Drug Dependence, 1996; Proceedings of the 58th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, in press.

  125. Spangler, R., Zhou, Y., Maggos, C. E., Schlussman, S., Ho, A. and Kreek, M. J. 1996. Pesistent 5preprodynorphin and kappa opioid receptor mRNA responses to cocaine occur acutely.in Harris, L. (ed.) Problems of Drug Dependence, 1996; Proceedings of the 58th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, in press.

  126. Hurd, Y. L., Herkenham, M. 1992. Influence of a single injection of cocaine, amphetamine or GBR 12909 on mRNA expression of striatal neuropeptides. Mol. Brain Res. 16:97–104.

    Article  PubMed  CAS  Google Scholar 

  127. Hurd, Y. L.; Brown, E. E.; Finlay, J. M.; Fibiger, H. C.; Gerfen, C. R. 1992. Cocaine self-administration differentially alters mRNA expression of striatal peptides. Mol. Brain Res. 13:165–170.

    Article  PubMed  CAS  Google Scholar 

  128. Daunais, J. B.; Roberts, D. C. S.; McGinty, J. F. 1993. Cocaine self-administration increases preprodynorphin, but not c-fos, mRNA in rat striatum. NeuroReport. 4:543–546.

    Article  PubMed  CAS  Google Scholar 

  129. Daunais, J. B.; McGinty, J. F. 1995. Cocaine binges differentially alter striatal preprodynorphin mRNA. Mol. Brain Res. 29:201–210.

    Article  PubMed  CAS  Google Scholar 

  130. LaForge, K. S., Unterwald, E. M., and Kreek, M. J. 1995. Structure and expression of the guinea pig preproenkephalin gene: Site-specific cleavage in the 3′ untranslated region yields truncated mRNA transcripts in specific brain regions. Mol. and Cell Biology. 15:2080–2089.

    CAS  Google Scholar 

  131. Yuferov, V. P., LaForge, K. S., Spangler, R., Maggos, C. E., and Kreek, M. J. 1996. Guinea pig preprodynorphin mRNA: Primary structure and regional quantitation in the brain. DNA and Cell Biology, in press.

  132. Yuferov, V., LaForge, K. S., Spangler, R., Ho, A. and Kreek, M. J. 1996. Regulation of guinea pig brain preprodynorphin mRNA expression by binge pattern cocaine administration.in Harris, L. (ed.) Problems of Drug Dependence, 1996; Proceedings of the 58th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, in press.

  133. Sivam, S. P. 1989. Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism. JPET. 250:818–824.

    CAS  Google Scholar 

  134. Chou, J. Z., Pinto, S., Kreek, M. J., and Chait, B. T. 1993. Study of opioid peptides by laser desorption mass spectrometry. Page 380,in Harris, L. S. (ed.), Problems of Drug Dependence, 1992; Proceedings of the 54th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, Supt. of Docs, U.S. Govt. Print. Off., DHHS Pub. No.(ADM) 93-3505, Washington, D.C.

  135. Kreek, M. J., Ho, A., and Borg, L., 1994. Dynorphin A1–13 administration causes elevation of serum levels of prolactin in human subjects. Page 108,in Harris, L. S. (ed.), Problems of Drug Dependence, 1993; Proceedings of the 55th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, Supt. of Docs., U.S., Govt. Print. Off., NIH Pub. No. 94-3749, Washington, D.C.

  136. Chou, J. Z., Chait, B. T., and Kreek, M. J. 1995. Study of dynorphin A peptidesin vitro processing in human blood by matrix-assisted laser desorption mass spectrometry. Page 252,in Harris, L. S. (ed.), Problems of Drug Dependence, 1994; Proceedings of the 56th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (ADM)95-3883, Washington, D.C.

  137. Butelman, E. R., Yu, J., Chou, J. Z., Chait, B. T., Kreek, M. J. and Woods, J. H. 1996. Dynorphin A (1–13): Biotransformation in human and rhesus monkey blood and antinociception. Page 225,in Harris, L. S. (ed.), Problems of Drug Dependence, 1995; Proceedings of the 57th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (ADM)96-4116, Washington, D.C.

  138. Yu, J., Butelman, E. R., Woods, J. H., Chait, B. T., and Kreek, M. J. 1996. Studies ofin vitro processing of dynorphin A (1–17) in human blood and in rhesus monkey blood. Page 131,in Harris, L. S. (ed.), Problems of Drug Dependence, 1995; Proceedings of the 57th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, Supt. of Docs., U.S. Govt. Print. Off., DHHS Pub. No. (ADM)96-4116, Washington, D.C.

  139. Claye, L. H., Maisonneuve, I. M., Yu, J., Ho, A. and Kreek, M. J. 1996. Local perfusion of dynorphin A(1–17) reduces extracellular dopamine levels in the nucleus accumbens.in Harris, L. (ed.) Problems of Drug Dependence, 1996; Proceedings of the 58th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute of Drug Abuse Research Monograph Series, in press.

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Special issue dedicated to Dr. Eric J. Simon.

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Kreek, M.J. Opioid receptors: Some perspectives from early studies of their role in normal physiology, stress responsivity, and in specific addictive diseases. Neurochem Res 21, 1469–1488 (1996). https://doi.org/10.1007/BF02532387

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