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Opioids pp 471-497 | Cite as

Anatomy and Function of the Endogenous Opioid Systems

  • H. Khachaturian
  • M. K. H. Schaefer
  • M. E. Lewis
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 104 / 1)

Abstract

The endogenous opioid systems constitute three distinct neuronal systems that are widely distributed throughout the central nervous system (CNS). The three opioid precursors found in these neurons, proopiomelanocortin (POMC), proenkephalin (PENK), and prodynorphin (PDYN), each contain numerous biologically active products that are released at the synaptic terminals of opioidergic neurons. These peptides exert their physiological actions by interacting with various classes of opioid receptor types (μ, δ, к) present on both pre- and postsynaptic membranes of opioid and opioid- target neurons. Opioid neurotransmission appears to influence many CNS functions, including nociception, cardiovascular regulation, respiration, neuroendocrine and neuroimmune activity, thermoregulation, and consummatory, sexual, aggressive, locomotor, and hedonic behavior, as well as learning and memory (Adler et al. 1988; Herz and Millan 1988; Khachaturian et al. 1988; Martinez et al. 1988; Pasternak 1988; Stefano 1989). Opioid peptides have also been implicated either directly or indirectly in the pathophysiology of several neurological, addictive, or psychiatric disorders, including Alzheimer’s, Parkinson’s, Huntington’s disease, stroke, epilepsy, brain and spinal cord injury, drug and alcohol addiction, eating disorders, manic-depressive illness, anxiety disorders, and schizophrenia (Nemeroff and Bissette 1986; Watson et al. 1986; Topel 1988; Kaye et al. 1989; Gulya 1990).

Keywords

Opioid Receptor Opioid Peptide Arcuate Nucleus Nucleus Tractus Solitarius Endogenous Opioid System 
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.

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References

  1. Abe J, Okamura H, Kitamura T, Ibata Y, Minamino N, Matsuo H, Paull WK (1988) Immunocytochemical demonstration of dynorphin(PH-8P)-like immunoreactive elements in the human hypothalamus. J Comp Neurol 276: 508–513PubMedGoogle Scholar
  2. Adler MW, Geller EB, Rosow CE, Cochin J (1988) The opioid system and tem¬perature regulation. Annu Rev Pharmacol Toxicol 28: 429–49PubMedGoogle Scholar
  3. Akil H, Mayer DJ, Liebeskind JC (1972) Comparison chez le rat entre l’analgesie induite par stimulation de la substance grise peri-aqueducale et l’analgesie morphinique. CR Acad Sci (Paris) 274: 3603–3605Google Scholar
  4. Akil H, Richardson DE, Barcgas JD, Li CH (1978) Appearance of beta-endorphin- like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation. Proc Natl Acad Sci USA 75: 5170–5172PubMedGoogle Scholar
  5. Akil H, Watson SJ, Young E, Lewis ME, Khachaturian H, Walker JM (1984) Endogenous opioids: biology and function. Annu Rev Neurosci 7: 223–255PubMedGoogle Scholar
  6. Alvarez BG, Fairen A, Dougless J, Naranjo JR (1990) Expression of the prodynorphin gene in the developing and adult cerebral cortex of the rat: an in situ hybridization study. J Comp Neurol 300: 287–300Google Scholar
  7. Angulo JA, Davis LG, Burkhart BA, Christoph GR (1986) Reduction of striatal dopaminergic neurotransmission elevates striatal pro-enkephalin mRNA. Eur J Pharmacol 130: 341–343PubMedGoogle Scholar
  8. Baldino F, Chesselet MF, Lewis ME (1989) High resolution in situ hybridization histochemistry. Methods Enzymol 168: 761–777PubMedGoogle Scholar
  9. Basbaum Al, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7: 309–234PubMedGoogle Scholar
  10. Bloom FE, Battenberg E, Rossier J, Ling N, Leppaluoto J, Vargo TM, Guillemin R (1977) Endorphins are located in the intermediate and anterior lobes of the pituitary gland, not in the neurohypophysis. Life Sci 20: 43–48PubMedGoogle Scholar
  11. Bloom FE, Battenberg E, Rossier J, Ling N, Guillemin R (1978) Neurons containing beta-endorphin exist separately from those containing enkephalin: immunocytochemical studies. Proc Natl Acad Sci USA 75: 1591–1595PubMedGoogle Scholar
  12. Blum M, Roberts JL, Wardlaw SL (1989) Androgen regulation of proopiomelanocortin expression and peptide content in the basal hypothalamus. Endocrinology 124: 2283–2288PubMedGoogle Scholar
  13. Bronstein DM, Przewlocki R, Akil H (1990) Effects of morphine treatment of proopiomelanocortin systems in rat brain. Brain Res 519: 102–111PubMedGoogle Scholar
  14. Buzzetti R, McLoughling R, Lavender PM, Clark AJ, Rees L (1989) Expression of proopiomelanocortin gene and quantification of adrenocorticotropic hormone like immunoreactivity in human normal peripheral mononuclear eels and lymphois and myeloid malignancies. J Clin Invest 83: 733–7838PubMedGoogle Scholar
  15. Cassell MD, Gray TS (1989) Morphology of peptide-immunoreactive neurons in the rat central nucleus of the amygdala. J Comp Neurol 281: 320–333PubMedGoogle Scholar
  16. Chavkin C, James I, Goldstein A (1982) Dynorphin is a specific endogenous ligand of the kappa opioid receptor. Science 215: 413–415PubMedGoogle Scholar
  17. Chesselet MF (1990) In situ hybridization histochemistry. CRC Press, Boca RatonGoogle Scholar
  18. Chesselet MF, Cheramy A, Reisine TD, Glowinski J (1981) Morphine and delta- opiate agonists locally stimulate in vivo dopamine release in cat caudate nucleus. Nature 291: 320–322PubMedGoogle Scholar
  19. Cho HJ, Basbaum Al (1988) Increased staining of immunoreactive dynorphin cell bodies in the deafferented spinal cord of the rat. Neurosci Lett 84: 125–130PubMedGoogle Scholar
  20. Chowen-Breed JA, Clifton DK, Steiner RA (1989a) Regional specificity of testosterone regulation of proopiomelanocortin gene expression in the arcuate nucleus of the male rat brain. Endocrinology 124: 2875–2881PubMedGoogle Scholar
  21. Chowen-Breed JA, Fraser HM, Vician L, Damassa DJ, Clifton DK, Steiner RA (1989b) Testosterone regulation of proopiomelanocortin messenger ribonucleic acid in the arcuate nucleus of the male rat. Endocrinology 124: 1697–1702PubMedGoogle Scholar
  22. Chung K, Briner RP, Carlton SM, Westlund KN (1989) Immunohistochemical localization of seven different peptides in the human spinal cord. J Comp Neurol 280: 158–170PubMedGoogle Scholar
  23. Civelli O, Birnberg N, Herbert E (1982) Detection and quantitation of proopiomelanocortin mRNA in pituitary and brain tissues from different species. J Biol Chem 257: 6783–6887PubMedGoogle Scholar
  24. Clouet DH, Ratner M (1970) Catecholamine biosynthesis in rats treated with morphine. Science 168: 854–856PubMedGoogle Scholar
  25. Comb M, Seeburg PH, Adelman J, Eiden L, Herbert E (1982) Primary structure of human Met- and Leu-enkephalin Precursor and its mRNA. Nature 295: 663–666PubMedGoogle Scholar
  26. Corbett AD, Peterson SJ, McKnight AT, Magnan J, Kosterlitz H (1982) Dynorphin (1–8) and dynorphin(1–9) are ligands for the kappa subtype of opiate receptor. Nature 299: 79–81PubMedGoogle Scholar
  27. Costall B, Fortune DH, Naylor RJ (1978) The induction of catalepsy and hyperactivity by morphine administered directly into the nucleus accumbens of rats. Eur J Pharmacol 49: 49–64PubMedGoogle Scholar
  28. Di Chiara G, Imperato A (1988) Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J Pharmacol Exp Ther 244: 1067–1080PubMedGoogle Scholar
  29. Dores RM, Akil H, Watson SJ (1984) Strategies for studying opioid peptide regulation at the gene, message, and protein levels. Peptides 5 (Suppl 1): 9–17PubMedGoogle Scholar
  30. Eberwine JH, Roberts JL (1984) Glucocorticoid regulation of proopiomelanocrotin gene transcription in the rat pituitary. J Biol Chem 259: 2166–2170PubMedGoogle Scholar
  31. Elde R, Hokfelt T, Johansson O, Terenius L (1976) Immunohistochemical studies using antibodies to leucine enkephalin: initial observations on the nervous system of the rat. Neuroscience 1: 349–351PubMedGoogle Scholar
  32. Fallon JH, Leslie FM (1986) Distribution of dynorphin and enkephalin peptides in the rat brain. J Comp Neurol 249:293-336 Fischli W, Goldstein A, Hunkapiller M, Hood L (1982) Two “big” dynorphins from porcine pituitary. Life Sci 31: 1769–1772Google Scholar
  33. Fremeau RT, Lundblad JR, Pritchett DB, Wilcox JN, Roberts JL (1986) Regulation of pro-opiomelanocortin gene transcription in individual cell nuclei. Science 234: 1265–1269PubMedGoogle Scholar
  34. Fremeau RT, Autelitano DJ, Blum M, Wilcox J, Roberts JL (1989) Intervening sequence-specific in situ hybridization: detection of the proopiomelanocortin gene primary transcript in individual neurons. Mol Brain Res 6: 197–201PubMedGoogle Scholar
  35. Gall C, Lauterborn J, Isackson P, White J (1990) Seizures, neuropeptide regulation,and mRNA expression in the hippocampus. Prog Brain Res 83: 371–390PubMedGoogle Scholar
  36. Gee C, Chen CLC, Roberts J, Thompson RC, Watson SJ (1983) Identification of proopiomelanocortin neurons in rat hypothalamus by in situ cDNA mRNA hybridization. Nature 374–376Google Scholar
  37. Goldstein A, Tachibana S, Lowney LI, Hunkapiller M, Hood L (1979) Dynorphin- (1–13), an extraordinarily potent opioid peptide. Proc Natl Acad Sci USA 76: 6666–6670PubMedGoogle Scholar
  38. Gerfen CR, Young WS (1988) Distribution of striatonigral and striatopallidal peptidergic neurons in both patch and matrix compartments: an in situ hybridization histochemistry and fluorescent retrograde tracing study. Brain Res 460: 161–167PubMedGoogle Scholar
  39. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ, Sibley DR (1990) Dl and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250: 1429–1432PubMedGoogle Scholar
  40. Gerfen CR, McGinty JF, Young WS III (1991) Dopamine differentially regulates dynorphin, substance P, and enkephalin expression in striatal neurons: in situ hybridization histochemical analysis. J Neurosci 11: 1016–1031PubMedGoogle Scholar
  41. Gubler U, Seeburg P, Hoffman BJ, Gage LP, Udenfriend S (1982) Molecular cloning establishes pro-enkephalin as precursor of enkephalin-containing peptides. Nature 295: 206–208PubMedGoogle Scholar
  42. Gulya K (1990) The opioid system in neurologic and psychiatric disorders and in their experimental models. Pharmacol Ther 46: 395–428PubMedGoogle Scholar
  43. Haber SN, Elde R (1982) The distribution of enkephalin immunoreactive fibers and minals in the monkey central nervous system. Neuroscience 7: 1049–1095PubMedGoogle Scholar
  44. Haber SN, Watson SJ (1985) The comparative distribution of enkephalin, dynorphin and substance P in the human globus pallidus and basal forebrain. Neuroscience 14: 1011–1024PubMedGoogle Scholar
  45. Hanson GR, Midgley LP, Bush LG, Johnson M, Gibb JW (1990) Comparison of responses by neuropeptide systems in rat to the psychotropic drugs, methamphetamine, cocaine and PCP. NIDA Res Monogr 95: 348Google Scholar
  46. Harlan RE, Shivers BD, Romano GJ, Howells RD, Pfaff DW (1987) Localization of proenkephaline mRNA in the rat brain and spinal cord by in situ hybridization. J Comp Neurol 258: 159–184PubMedGoogle Scholar
  47. Hauser KF, Osborne JG, Stiene MA, Melner MH (1990) Cellular localization of proenkephaline mRNA and enkephalin peptide products in cultured astrocytes. Brain Res 522: 347–353PubMedGoogle Scholar
  48. Haynes LW, Smyth DG, Zakarian S (1982) Immunocytochemical localization of β-endorphin (lipotropin C fragment) in the developing rat spinal cord and hypothalamus. Brain Res 232: 115–128PubMedGoogle Scholar
  49. Herkenham M (1987) Mismatches between neurotransmitter and receptor localizations in brain: observations and implications. Neuroscience 23: 1–38PubMedGoogle Scholar
  50. Herz A, Millan MJ (1988) Endogenous opioid peptides in the descending control of nociceptive responses of spinal dorsal horn neurons. Prog Brain Res 77: 263–273PubMedGoogle Scholar
  51. Hökfelt T, Holets VR, Staines W, Meister B, Melander T, Schalling M, Schultzberg M, Freedman J, Bjorklund H, Olson L, Lindh B, Elfvin L-G, Lundberg JM, Lindgren J A, Samuelsson B, Pernow B, Terenius L, Post C, Everitt B, Goldstein M (1986) Coexistence of neuronal messengers — an overview. Prog Brain Res 68: 33–70PubMedGoogle Scholar
  52. Holaday JW, Tortella FC, Meyerhoff JL, Belenky GL, Hitzenmann RJ (1986) Electroconvulsive shock activates endogenous opioid systems: behavioral and biochemical correlates. Ann N Y Acad Sci 467: 249–255PubMedGoogle Scholar
  53. Höllt V, Haarmann I, Millan MJ, Herz A (1987) Prodynorphine gene expression is enhanced in the spinal cord of chronic arthritic rats. Neurosci Lett 73: 90–94PubMedGoogle Scholar
  54. Höllt V, Haarmann I, Reimer S (1989) Opioid gene expression in rats after chronic morphine treatment. Adv Biosci 75: 711–714Google Scholar
  55. Hong JS, Yoshikawa K, Kanamatsu T, Sabol SL (1985) Modulation of striatal enkephalinergic neurons by antipsychotic drugs. Fed Proc 44: 1535–2539Google Scholar
  56. Hong JS, Grimes L, Kanamatsu T, McGinty JF (1987) Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus. Toxicology 46: 141–157PubMedGoogle Scholar
  57. Hong JS, McGinty JF, Grimes L, Kanamatsu T, Obie J, Mitchell CL (1988) Seizure induced alterations in the metabolism of hippocampal opioid peptides suggest opioid modulation of seizure related behavior. NIDA Res Monogr Ser 82: 48–46Google Scholar
  58. Hosobuchi Y, Adams JE, Linchitz R (1977) Pain relief by electrical stimulation of the central grey matter in humans and its reversal by naloxone. Science 197: 183–186PubMedGoogle Scholar
  59. Hosobuchi Y, Rossier J, Bloom FE, Guillemin R (1979) Stimulation of human periaqueductal grey for pain relief increases immunoreactive beta-endorphin in ventricular fluid. Science 203: 279–281PubMedGoogle Scholar
  60. Hughes J, 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: 577–579PubMedGoogle Scholar
  61. Iadarola MJ, Douglas J, Civelli O, Naranjo JR (1986) Increased spinal cord dynorphin mRNA during peripheral inflammation. NIDA Res Monogr Ser 75: 406–409Google Scholar
  62. Iadarola MJ, Douglass J, Civelli O, Naranjo JR (1988) Differential activation of spinal cord dynorphin and enkephalin neurons during hyperalgesia: evidence using cDNA hybridization. Brain Res 455: 205–212PubMedGoogle Scholar
  63. Ibuki T, Okamura H, Miyazaki M, Kimura H, Yanaihara N, Ibata Y (1988) Colocalization of GABA and [Met]enkephalin-Arg6-Gly7-Leu8 in the rat cerebellum. Neurosci Lett 91: 131–135PubMedGoogle Scholar
  64. Ibuki T, Okamura H, Miyazaki M, Yanaihara N, Zimmerman EA, Ibata Y (1989) Comparative distribution of three opioid systems in the lower brainstem of the monkey (Macaca fasciculata). J Comp Neurol 279: 445–456PubMedGoogle Scholar
  65. Illes P (1989) Modulation of transmitter and hormone release by multiple neuronal opioid receptors. Rev Physiol Biochem Pharmacol 112: 139–233PubMedGoogle Scholar
  66. Ito M (1984) The cerebellum and neural control. Raven, New YorkGoogle Scholar
  67. Jackson A, Cooper SJ (1988) Observational analysis of the effects of kappa opioid agonists on open field behaviour in the rat. Psychopharmacology (Berl) 94: 248–253Google Scholar
  68. Jiang H-K, McGinty JF, Hong JS (1990) Differential modulation of striatonigral dynorphin and enkephalin by dopamine receptor subtypes. Brain Res 507: 57–64PubMedGoogle Scholar
  69. Joyce EM, Iversen SD (1979) The effect of morphine applied locally to mesencephalic dopamine cell bodies on spontaneous motor activity in the rat. Neurosci Lett 14: 207–212PubMedGoogle Scholar
  70. Kakidani H, Furutani Y, Takahashi H, Noda M, Morimoto Y, Hirose T, Asai M, Inayama S, Nakanishi S, Numa S (1982) Cloning and sequence analysis of cDNA for porcine beta-neo-endorphin/dynorphin precursor. Nature 298: 245–249PubMedGoogle Scholar
  71. Kangawa K, Minamino N, Chino N, Sakakibara S, Matsuo H (1981) The complete amino acid sequence of alpha-neo-endorphin. Biochem Biophys Res Commun 99: 871–878PubMedGoogle Scholar
  72. Kaye WH, Berrettini WH, Gwirtsman HE, Gold PW, George DT, Jimerson DC, Ebert MH (1989) Contribution of CNS neuropeptide (NPY, CRH, and beta- endorphin) alterations to psychophysiological abnormalities in anorexia nervosa. Psychopharmacol Bull 25: 433–438Google Scholar
  73. Khachaturian H, Watson SJ (1982) Some perspectives on monoamine-opioid peptide interactions in rat central nervous system. Brain Res Bull 9: 441–462PubMedGoogle Scholar
  74. Khachaturian H, Watson SJ, Lewis ME, Coy DH, Goldstein A, Akil H (1982) Dynorphin peptide immunocytochemistry in the rat central nervous system. Peptides 3: 941–954PubMedGoogle Scholar
  75. Khachaturian H, Lewis ME, Höllt V, Watson SJ (1983a) Telencephalic enkephalinergic systems in the rat brain. J Neurosci 3: 844–855PubMedGoogle Scholar
  76. Khachaturian H, Lewis ME, Watson SJ (1983b) Enkephalin systems in diencephalon and brainstem of the rat. J Comp Neurol 220: 310–320PubMedGoogle Scholar
  77. Khachaturian H, Lewis ME, Watson SJ (1983c) Colocalization of pro-enkephalin peptides in rat brain neurons. Brain Res 279: 369–373PubMedGoogle Scholar
  78. Khachaturian H, Lewis ME, Haber SN, Akil H, Watson SJ (1984) Pro-opiomelanocortin peptide immunocytochemistry in rhesus monkey brain. Brain Res Bull 13: 785–800PubMedGoogle Scholar
  79. Khachaturian H, Lewis ME, Haber SN, Houghten RA, Akil H, Watson SJ (1985a) Pro-dynorphin peptide immunocytochemistry in rhesus monkey brain. Peptides 6 (Suppl 2): 155–166PubMedGoogle Scholar
  80. Khachaturian H, Lewis ME, Schäfer M-KH, Watson SJ (1985b) Anatomy of CNS opioid systems. Trends Neurosci 8: 111–119Google Scholar
  81. Khachaturian H, Lewis ME, Tsou K, Watson SJ (1985c) β-Endorphin a-MSH, ACTH, and related peptides. In: Bjorklund A, Hokfelt T (eds) GABA and neuropeptides in CNS, part I. Elsevier, Amsterdam, pp 216–272 (Handbook of chemical neuroanatomy, vol 4)Google Scholar
  82. Khachaturian H, Sherman TG, Lloyd RV, Civelli O, Douglas J, Herbert E, Akil H, Watson SJ (1986) Pro-dynorphin is endogenous to the anterior pituitary and is co-localized with LH and FSH in the gonadotrophs. Endocrinology 119: 1409–1411PubMedGoogle Scholar
  83. Khachaturian H, Day R, Watson SJ, Akil H (1988) Opioid peptides in the hypothalamus-pituitary-adrenal axis: neuroendocrine anatomy. In: Barchas JD, Bunney WE (ed) Perspectives in psychopharmacology: a collection of papers in honor of Earl Usdin. Liss, New York, pp 233–247Google Scholar
  84. Kilpatrick DL, Wahlstrom A, Lahm HW, Blacher R, Udenfriend S (1982) Rimorphin, a unique, naturally occurring [Leu]enkephalin-containing peptide found in association with dynorphin and alpha-neo-endorphin. Proc Natl Acad Sci USA 79: 6480–6483PubMedGoogle Scholar
  85. Kirby ML, Mattio TG (1982) Developmental changes in serotonin and 5- hydroxyindolacetic acid concentrations and opiate receptor binding in rat spinal cord following neonatal 5,7-dihydroxytryptamine treatment. Dev Neurosci 5: 394–402PubMedGoogle Scholar
  86. Lauber AH, Romano GJ, Mobbs CV, Howells RD, Pfaff DW (1990) Estradiol induction of proenkephalin messenger RNA in hypothalamus: dose-response and relation to reproductive behavior in the female rat. Brain Res Mol Brain Res 8: 47–54PubMedGoogle Scholar
  87. Lewis JW, Canno JT, Chudler EH, Liebeskind JC (1981) Effects of naloxone and hypophysectomy on electroconvulsive shock-induced analgesia. Brain Res 208: 230–233PubMedGoogle Scholar
  88. Lewis ME, Krause RG II, Roberts-Lewis JM (1988) Recent developments in the use of synthetic oligonucleotides for in situ hybridization histochemistry. Synapse 2: 308–316PubMedGoogle Scholar
  89. Li CH, Chung D (1976) Isolation and structure of a triakontapeptide with opiate activity from camel pituitary glands. Proc Natl Acad Sci USA 73: 1145–1148PubMedGoogle Scholar
  90. Li SJ, Sivam SP, Hong JS (1986) Regulation of the concentration of dynorphin A(1–8) in the striatonigral pathway by the dopaminergic system. Brain Res 398: 390–392PubMedGoogle Scholar
  91. Li SJ, Sivam SP, McGinty JF, Jiang HK, Douglass J, Calavetta L, Hong JS (1988) Regulation of the metabolism of striatal dynorphin by the dopaminergic system. J Pharmacol Exp Therap 246: 403–408Google Scholar
  92. Lightman SL, Young WS (1987) Changes in hypothalamic preproenkephalin A mRNA following stress and opiate withdrawal. Nature 328: 643–645PubMedGoogle Scholar
  93. Loh HH, Smith AP (1990) Molecular characterization of opioid receptors. Annu Rev Pharmacol Toxicol 30: 123–147PubMedGoogle Scholar
  94. Mains RE, Eipper EA, Ling N (1977) Common precursor to corticotropins and endorphins. Proc Natl Acad Sci USA 74: 3014–3018PubMedGoogle Scholar
  95. Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ (1988) Anatomy of CNS opioid receptors. Trends Neurosci 11: 308–314PubMedGoogle Scholar
  96. Martinez JL Jr, Weinberger SB, Schulteis G (1988) Enkephalins and learning and memory: a review of evidence for a site of action outside the blood-brain barrier. Behav Neural Biol 49: 192–221PubMedGoogle Scholar
  97. Mathiasen JR, Vaught JL (1987) [D-Pen2, L-Pen5]enkephalin induced analgesia in the jimpy mouse: in vivo evidence for delta-receptor mediated analgesia. Eur J Pharmacol 136:405–407PubMedGoogle Scholar
  98. Mayer DJ, Hayes RL (1975) Stimulation-produced analgesia: development of tolerance and cross-tolerance to morphine. Science 188: 941–943PubMedGoogle Scholar
  99. Mayer DJ, Wolfle TL, Akil H, Carder B, Liebeskind JC (1971) Analgesia from electrical stimulation in the brainstem of the rat. Science 174: 1351–1354PubMedGoogle Scholar
  100. McCabe JT, Desharnais RA, Pfaff DW (1989) Graphical and statistical approaches to data analysis for in situ hybridization. Methods Enzymol 168: 822–848PubMedGoogle Scholar
  101. McDowell J, Kitchen I (1987) Development of opioid systems: peptides, receptors and pharmacology. Brain Res Rev 12: 397–421Google Scholar
  102. McGinty JF, van der Kooy D, Bloom FE (1984) The distribution and morphology of opioid peptide immunoreactive neurons in the cerebral cortex of rats. J Neurosci 4: 1104–1117PubMedGoogle Scholar
  103. McLean S, Rothman RB, Chuang DM, Rice KC, Spain JW, Coscia CJ, Roth BL (1989) Cross-linking of [125I]beta-endorphin to mu-opioid receptors during development. Dev Brain Res 45: 283–289Google Scholar
  104. Melner MH, Low KG, Allen RG, Nielsen CP, Young SL, Saneto RP (1990) The regulation of proenkephalin expression in a distinct population of glial cells. EMBO J 9: 791–796PubMedGoogle Scholar
  105. Millan MJ (1990) Kappa-opioid receptors and analgesia. Trends Pharmacol Sci 11: 7076Google Scholar
  106. Millan MJ, Weihe E, Czlonkowski AC (1991) Endogenous opioid systems in the control of pain. In: Almeida OF, Shippenberg TS (eds) Neurobiology of opioids. Springer, Berlin Heidelberg New York, pp 245–260Google Scholar
  107. Miller KE, Seybold VM (1989) Comparison of Met-enkephalin, dynorphin A, and neurotensin immunoreactive neurons in the cat and rat spinal cords: II. Segmental differences in the marginal zone. J Comp Neurol 279: 619–628Google Scholar
  108. Milner TA, Pickel VM, Reis DJ (1989) Ultrastructural basis for interactions between central opioids and catecholamines: I. Rostral ventrolateral medulla. J Neurosci 9: 2114–2130Google Scholar
  109. Mocchetti I, Ritter A, Costa E (1989) Down-regulation of proopiomelanocortin synthesis and beta-endorphin utilization in hypthalamus of morphine-tolerant rats. J Mol Neurosci 1: 33–38PubMedGoogle Scholar
  110. Moon SL (1984) Prenatal haloperidol alters striatal dopamine and opiate receptors. Brain Res 323: 109–113PubMedGoogle Scholar
  111. Moon Edley S, Hall SL, Herkenham M, Pert CB (1982) Evolution of striatal opiate receptors. Brain Res 249: 184–188Google Scholar
  112. Morris BJ, Haarmann I, Kempter B, Höllt V, Herz A (1986) Localization of prodynorphin messenger RNA in rat brain by in situ hybridization using a synthetic oligonucleotide probe. Neurosci Lett 69: 104–108PubMedGoogle Scholar
  113. Morris BJ, Feasey KJ, Ten BG, Herz A, Höllt V (1988a) Electrical stimulation in vivo increases the expression of proenkephalin mRNA and decreases the expression of prodynorphin mRNA in rat hippocampal granule cells. Proc Natl Acd Sci USA 85: 3226–3230Google Scholar
  114. Morris BJ, Höllt V, Herz A (1988b) Dopaminergic regulation of striatal proenkephalin mRNA and prodynorphin mRNA: contrasting effects of D1 and D2 anatgonists. Neuroscience 25: 525–532PubMedGoogle Scholar
  115. Morris BJ, Herz A, Höllt V (1989) Localization of striatal opioid gene expression, and its modulation by the mesostriatal dopamine pathway; an in situ hybridization study. J Mol Neurosci 1: 9–18PubMedGoogle Scholar
  116. Mulcahy J, Lee HS, Basbaum Al (1983) Coexistence of immunoreactive enkephalin (I-Enk) and dynorphin ( I-Dyn) in the nucleus of the solitary tract of the rat. Soc Neurosci Abstr 9: 439Google Scholar
  117. Murakami S, Okamura H, Pelletier G, Ibata Y (1989) Differential colocalization of neuropeptide Y- and methionine-enkephalin-Arg6-Gly7-Leu8-like immuno- reactivity in catecholaminergic neurons in the rat brain stem. J Comp Neurol 281: 532–544PubMedGoogle Scholar
  118. Nahin RL (1988) Immunocytochemical identification of long ascending, peptidergic lumbar spinal neurons terminating in either the medial or lateral thalamus in the rat. Brain Res 443: 345–349PubMedGoogle Scholar
  119. Nakanishi S, Inoue A, Kita T, Nakamura M, Chang ACY, Cohen S, Numa S (1979) Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor. Nature 278: 423–427PubMedGoogle Scholar
  120. Nemeroff CB, Bissette G (1986) Neuropeptides in psychiatric disorders. In: Berger PA, Brodie KH (eds) American handbook of psychiatry, 2nd edn. Basic Books, New York, pp 64–110Google Scholar
  121. Noda M, Furutani Y, Takahashi H, Toyosato M, Hirose T, Inayama S, Numa S (1982) Cloning and sequence analysis of cDNA for bovine adrenal pre-pro- enkephalin. Nature 295: 202–206PubMedGoogle Scholar
  122. Olson GA, Olson RD, Kastin AJ (1989) Endogenous opiates: 1988. Peptides 10: 1253–1280PubMedGoogle Scholar
  123. Pasternak GW (1988) Multiple morphine and enkephalin receptors and the relief of pain. JAMA 259: 1362–1367PubMedGoogle Scholar
  124. Petrusz P, Merchenthaler I, Maderdrut JL (1985) Distribution of enkephalin- containing neurons in the central nervous system. In: Bjorklund A, Hokfelt T (eds) GAB A and neuropeptides in CNS, part I. Elsevier, Amsterdam, pp 273–334 (Handbook of chemical neuroanatomy, vol 4 )Google Scholar
  125. Pickel VM, Chan J, Milner TA (1989) Ultrastructural basis for interactions between central opioids and catecholamines: II. Nuclei of the solitary tract. J Neurosci 9: 2519–2535Google Scholar
  126. Pilapil C, Welner S, Magnan J, Gauthier S, Quirion R (1987) Autoradiographic distribution of multiple classes of opioid receptor binding sites in human forebrain. Brain Res Bull 19: 611–615PubMedGoogle Scholar
  127. Polakiewicz RD, Rosen H (1990) Regulated expression of proenkephalin A during ontogenic development of mesenchymal derivative tissues. Mol Cell Biol 10: 736–742PubMedGoogle Scholar
  128. Quirion R, Weiss AS (1983) Peptide E and other pro-enkephalin-derived peptides are kappa opiate receptor agonists. Peptides 4: 445–449Google Scholar
  129. Reis DJ, Hess P, Azmitia E (1970) Changes in enzymes subserving catecholamine metabolism in morphine tolerance and withdrawal in rat. Brain Res 20: 309–312PubMedGoogle Scholar
  130. Richardson DE, Akil H (1977a) Pain reduction by electrical brain stimulation in man: 1. Acute administration in periaqueductal and periventricular sites. J Neurosurg 47: 184–194Google Scholar
  131. Richardson DE, Akil H (1977b) Pain reduction by electrical brain stimulation in man: 2. Chronic self-administration in the periventricular grey matter. J Neurosurg 47: 184–194Google Scholar
  132. Roberts JL, Herbert E (1977) Characterization of a common precursor to corticotropin and beta-lipotropin: identification of beta-lipotropin peptides and their arrangement relative to corticotropin in the precursor synthesized in a cell-free system. Proc Natl Acad Sci USA 74: 5300–5304PubMedGoogle Scholar
  133. Romano GJ, Shivers BD, Harlan RE, Howells RD, Pfaff DW (1987) Haloperidol increases pro-enkephalin mRNA levels in the caudate-putamen of the rat: a quantitative study at the cellular level using in situ hybridization. Mol Brain Res 2: 33–41Google Scholar
  134. Romano GJ, Mobbs CV, Howells RD, Pfaff DW (1989) Estrogen regulation of proenkephalin gene expression the ventromedial hypothalamus of the rat: temporal qualities and synergism with progesterone. Brain Res Mol Brain Res 5: 51–58PubMedGoogle Scholar
  135. Romano GJ, Mobbs CV, Lauber A, Howells RD, Pfaff DW (1990) Differential regulation of proenkephalin gene expression by estrogen in the ventromedial hypthalamus of male and female rats: implications for the molecular basis of a sexually differentiated behavior. Brain Res 536: 63–68PubMedGoogle Scholar
  136. Rosen H, Behar O, Abramsky O, Ovadia H (1989) Regulated expression of proenkephalin A in normal lymphocytes. J Immunol 143: 3703–3707PubMedGoogle Scholar
  137. Rougeot C, Charnay Y, Dray F, Dubois PM (1988) Chromatographic identification of Met- and Leu-enkephalin in the human fetal spinal cord. Peptides 9: 125–131PubMedGoogle Scholar
  138. Ruda MA, Iadarola MJ, Cohen LV, Young WS (1988) In situ hybridization histochemistry and immunocytochemistry reveal an increase in spinal dynorphin biosynthesis in a rat model of peripheral inflammation and hyperalgesia. Proc Natl Acad Sci USA 85: 622–626PubMedGoogle Scholar
  139. Sabol SL, Yoshikawa K, Hong JS (1983) Regulation of methionine-enkephalin precursor messenger RNA in rat striatum by haloperidol and lithium. Biochem Biophys Res Commun 113: 391–399PubMedGoogle Scholar
  140. Sasek CA, Elde RP (1986) Coexistence of enkephalin and dynorphin immuno- reactivities in neurons in the dorsal gray commissure of the sixth lumbar and first sacral spinal cord segments in rat. Brain Res 381: 8–14PubMedGoogle Scholar
  141. Schäfer MK-H, Day R, Herman JP, Kwasiborski V, Sladek CD, Akil H, Watson SJ (1989) Effect of electroconvulsive shock on dynorphin in the hypothalamic- neurohypophysial system of the rat. Adv Biosci 75: 599–602Google Scholar
  142. Schäfer MK-H, Day R, Ortega MR, Akil H, Watson SJ (1990a) Proenkephalin messenger RNA is expressed both in the rat anterior and posterior pituitary. Neuroendocrinology 51: 444–448PubMedGoogle Scholar
  143. Schäfer MK-H, Herman JP, Thompson RC, Watson SJ (1990b) In situ detection of POMC heteronuclear RNA in individual nuclei in rat brain and pituitary. Soc Neurosci Abstr 20: 1276Google Scholar
  144. Schäfer MK-H, Day R, Watson SJ, Akil H (1991) Distribution of opioids in brain and peripheral tissues. In: Almeida OF, Shippenberg TS (eds) Neurobiology of opioids. Springer, Berlin Heidelberg New York, pp 53–71Google Scholar
  145. Schwartzberg DG, Nakane PK (1983) ACTH-related peptide containing neurons within the medulla oblongata of the rat. Brain Res 276: 351–356PubMedGoogle Scholar
  146. Seizinger BR, Grimm C, Höllt V, Herz A (1983) Evidence for a selective processing of pro-enkephalin B into different opioid peptide forms in particular regions of rat brain and pituitary. J Neurochem 42: 447–457Google Scholar
  147. Senba E, Yanaihara C, Yanaihara N, Tohyama M (1988) Co-localization of substance P and Met-enkephalin-Arg6-Gly7-Leu8 in the intraspinal neurons of the rat, with special reference to the neurons in the substantia gelatinosa. Brain Res 453: 110–116PubMedGoogle Scholar
  148. Sherman TG, Civelli O, Douglass J, Herbert E, Burke S, Watson SJ (1986) Hypothalamic dynorphin and vasopressin mRNA expression in normal and Brattelboro rats. Fed Proc 45: 2323–2327PubMedGoogle Scholar
  149. Shinoda H, Marini AM, Cosi C, Schwartz JP (1989) Brain region and gene specificity of neuropeptide gene expression in cultured astrocytes. Science 245: 415–417PubMedGoogle Scholar
  150. Shinoda K, Michigami T, Awanr K, Shiotani Y (1988) Analysis of the rat interpeduncular subnuclei by immunocytochemical double-staining for enkephalin and substance P, with reference to the coexistence of both peptides. J Comp Neurol 271: 243–256PubMedGoogle Scholar
  151. Simerly RB, McCall LD, Watson SJ (1988) Distribution of opioid peptides in the preoptic region: immunohistochemical evidence for a steroid-sensitive enkephalin sexual dimorphism. J Comp Neurol 276: 442–459PubMedGoogle Scholar
  152. Sivam SP, Strunk C, Smith DR, Hong JS (1986) Pro-enkephalin-A gene regulation in the rat striatum: influence of lithium and haloperidol. Mol Pharmacol 30: 186–191PubMedGoogle Scholar
  153. Smith CB, Villarreal JE, Bednarczyk JH, Sheldon MI (1970) Tolerance to morphine- induced increases in (11C) catecholamine synthesis in mouse brain. Science 170: 1106–1108PubMedGoogle Scholar
  154. Smith EM, Morill AC, Meyer WJ, Blalock JE (1986) Corticotropin releasing factor induction of leucocyte-derived immunoreactive ACTH and endorphins. Nature 321: 881–882PubMedGoogle Scholar
  155. Spruce BA, Curtis R, Wilkin GP, Glover DM (1990) A neuropeptide precursor in cerebellum: proenkephalin exists in subpopulations of both neurons and astrocytes. EMBO J 9: 1787–1795PubMedGoogle Scholar
  156. Stefano GB (1989) Role of opioid neuropeptides in immunoregulation. Prog Neurobiol 33: 149–159PubMedGoogle Scholar
  157. Stengaard-Pedersen K (1989) Opioid peptides and receptors. Localization, interactions and relationships to other molecules in the rodent brain, especially the hippocampal formation. Prog Histochem Cytochem 20: 1–119PubMedGoogle Scholar
  158. Tang F, Costa E, Schwartz JP (1983) Increase of proenkephalin mRNA and enkephalin content of rat striatum after daily injection of haloperidol for 2 to 3 weeks. Proc Natl Acad Sci USA 80: 3841–3844PubMedGoogle Scholar
  159. Thompson LA, Matsumoto RR, Hohmann AG, Walker JM (1990) Striatonigral prodynorphin: a model system for understanding opioid peptide function. Ann NY Acad Sci 579: 192–203PubMedGoogle Scholar
  160. Topel H (1988) Beta-endorphin genetics in the etiology of alcoholism. Alcohol 5: 159–165PubMedGoogle Scholar
  161. Trujillo KA, Akil H (1990) Changes in pro-dynorphin peptide content following treatment with morphine or amphetamine: possible role in mechanisms of action of drug of abuse. NIDA Res Monogr 95: 550–551Google Scholar
  162. Tsou K, Khachaturian H, Akil H, Watson SJ (1986) Immunocytochemical localization of pro-opiomelanocortin-derived peptides in the adult rat spinal cord. Brain Res 378: 28–35PubMedGoogle Scholar
  163. Tuchscherer MM, Seybold VM (1989) A quantitative study of the coexistence of peptides in varicosities within the superficial laminae of the dorsal horn of the rat spinal cord. J Neurosci 9: 195–205PubMedGoogle Scholar
  164. Uhl G (1986) In situ hybridization in brain. Plenum, New YorkGoogle Scholar
  165. Valentino KL, Eberwine JH, Barchas JD (1987) In situ hybridization: applications to neurobiology. Oxford University Press, OxfordGoogle Scholar
  166. Vilijn MH, Vaysse PJ, Zukin RS, Kessler JA (1988) Expression of preproenkephalin mRNA by cultured astrocytes and neurons. Proc Natl Acad Sci USA 85: 6551–6555PubMedGoogle Scholar
  167. Vincent SR, Hokfelt T, Christensson I, Terenius L (1982) Dynorphin immunoreactive neurons in the central nervous system of the rat. Neurosci Lett 33: 185–190PubMedGoogle Scholar
  168. Walker JM, Thompson LA, Frascella J, Friederich MW (1987) Opposite effects of mu and kappa opiate on the firing rate of dopamine cells in the substantia nigra of the rat. Eur J Pharmacol 134: 53–59PubMedGoogle Scholar
  169. Walker LC, Koliatsos VE, Kitt CA, Richardson RT, Rokaeus A, Price DL (1989) Peptidergic neurons in the basal forebrain magnocellular complex of the rhesus monkey. J Comp Neurol 280: 272–282PubMedGoogle Scholar
  170. Watson SJ, Akil H (1980) Alpha-MSH in rat brain: occurrence within and outside brain beta-endorphin neurons. Brain Res 182: 217–223PubMedGoogle Scholar
  171. Watson SJ, Akil H, Richard CW, Barchas JD (1978a) Evidence for two separate opiate peptide neuronal systems. Nature 275: 226–228PubMedGoogle Scholar
  172. Watson SJ, Richard CW, Barchas JD (1978b) Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons. Science 200: 1180–1182PubMedGoogle Scholar
  173. Watson SJ, Akil H, Ghazarossian VE, Goldstein A (1981) Dynorphin immunocytochemical localization in brain and peripheral nervous system. Proc Natl Acad Sci USA 78: 1260–1263PubMedGoogle Scholar
  174. Watson SJ, Akil H, Fischli W, Goldstein A, Zimmerman E, Nilaver G, van Wimersma Greidanus TB (1982a) Dynorphin and vasopressin: common localization in magnocellular neurons. Science 216: 85–87PubMedGoogle Scholar
  175. Watson SJ, Khachaturian H, Akil H, Coy DH, Goldstein A (1982b) Comparison of the distribution of dynorphin systems and enkephalin systems in brain. Science 218: 1134–1136PubMedGoogle Scholar
  176. Watson SJ, Khachaturian H, Taylor L, Fischli W, Goldstein A, Akil H (1983) Pro-dynorphin peptides are found in the same neurons throughout rat brain: immunocytochemical study. Proc Natl Acad Sci USA 80: 891–894PubMedGoogle Scholar
  177. Watson SJ, Khachaturian H, Lewis ME, Akil H (1986) Chemical neuroanatomy as a basis for biological psychiatry. In: Berger PA, Brodie KH (eds) American handbook of psychiatry, 2nd edn. Basic Books, New York, pp 3–33Google Scholar
  178. Watson SJ, Sherman TG, Schäfer MK-H, Patel P, Herman JP, Akil H (1988) Regulation of mRNA in peptidergic systems: quantitative and in situ studies. In: Chretien M, McKerns KW (eds) Molecular biology of brain and endocrine peptidergic systems. Plenum, New York, pp 225–241Google Scholar
  179. Weber E, Barchas JD (1983) Immunocytochemical distribution of dynorphin B in rat brain: relation to dynorphin A and alpha-neo-endorphin. Proc Natl Acad Sci USA 80: 1125–1129PubMedGoogle Scholar
  180. Weber E, Evans CJ, Barchas JD (1982) Predominance of the amino-terminal beta- peptide fragment of dynorphin in rat brain regions. Nature 299: 77–79PubMedGoogle Scholar
  181. Weihe E, Nohr D, Hartschuh W (1988a) Immunohistochemical evidence for a co-transmitter role of opioid peptides in primary sensory neurons. Prog Brain Res 74: 189–199PubMedGoogle Scholar
  182. Weihe E, Nohr D, Millan MJ, Stein C, Mueller S, Gramsch C, Herz A (1988b) Peptide neuroanatomy of adjuvant-induced arthritic inflammation in rat. Agents Actions 25: 255–259PubMedGoogle Scholar
  183. Weihe E, Milan MJ, Höllt V, Nohr D, Herz A (1989) Induction of the gene encoding prodynorphin by experimentally induced arthritis enhances staining for dynorphin in the spinal cord of rats. Neuroscience 31: 77–95PubMedGoogle Scholar
  184. Weihe E, Nohr D, Michel S, Muller S, Zentel H-H, Fink T, Krekel J (1992) Molecular anatomy of the neuroimmune connection. Int J Neurosci (in press)Google Scholar
  185. White JD, Gall CM, McKelvy JF (1986) Pro-enkephalin is processed in a projection- specific manner in the rat central nervous system. Proc Natl Acad Sci USA 83: 7099–7103PubMedGoogle Scholar
  186. Wiemann JN, Clifton DK, Steiner RA (1989) Pubertal changes in gonadotropin- releasing hormone and proopiomelanocortin gene expression in the brain of the male rat. Endocrinology 124: 1760–1767PubMedGoogle Scholar
  187. Wilcox JN, Roberts JL (1985) Estrogen decreases rat hypothalamic proopiomelanocortin messenger ribonucleic acid levels. Endocrinology 117: 2392–2396PubMedGoogle Scholar
  188. Xie CW, Lee PHK, Takeuchi K, Owyang V, Li SJ, Douglass J, Hong JS (1989) Single or repeated electroconvulsive shocks alter the levels of pro-dynorphin and pro-enkephalin mRNAs in rat brain. Mol Brain Res 6: 11–19PubMedGoogle Scholar
  189. Yoshida M, Taniguchi Y (1988) Projection of pro-opiomelanocortin neurons from the rat arcuate nucleus to the midbrain central gray as demonstrated by double label staining with retrograde labeling and immunohistochemistry. Arch Histol Cytol 51: 175–183PubMedGoogle Scholar
  190. Young EA, Walker JM, Lewis ME, Houghten RA, Woods JH, Akil H (1986) [3H]Dynorphin A binding and selectivity of pro-dynorphin peptides in rat, guinea-pig and monkey brain. Eur J Pharmacol 121:355–365PubMedGoogle Scholar
  191. Young WS (1990) In situ hybridization histochemistry. In: Hokfelt T (ed) Handbook of chemical neuroanatomy, vol 7. Elsevier, Amsterdam, pp 481–512Google Scholar
  192. Young WS, Bonner TI, Brann MR (1986) Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain. Proc Natl Acad Sci USA 83: 9827–9831PubMedGoogle Scholar
  193. Zagon DS, Rhodes RE, McLaughlin PJ (1985) Distribution of enkephalin immuno- reactivity in germinativa cells of developing rat cerebellum. Science 227: 1049–1051PubMedGoogle Scholar
  194. Zardetto-Smith AM, Moga MM, Magnuson DJ, Gray TS (1988) Lateral hypothalamic dynorphinergic efferents to the amygdala and brainstem in rat. Peptides 9: 1121–1127PubMedGoogle Scholar
  195. Zurawski G, Benedik M, Kamb BJ, Abrams JS, Zurawski SM, Lee FD (1986) Activation of mouse T-helper cells induces abundant preproenkephalin mRNA synthesis. Science 232: 772–775PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • H. Khachaturian
  • M. K. H. Schaefer
  • M. E. Lewis

There are no affiliations available

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