Skip to main content
SpringerLink
Log in

Anatomy and Function of the Endogenous Opioid Systems

  • Chapter
Opioids

Part of the book series: Handbook of Experimental Pharmacology ((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).

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • 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: 508–513

    PubMed  CAS  Google Scholar 

  • Adler MW, Geller EB, Rosow CE, Cochin J (1988) The opioid system and tem¬perature regulation. Annu Rev Pharmacol Toxicol 28: 429–49

    PubMed  CAS  Google Scholar 

  • 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: 3603–3605

    CAS  Google Scholar 

  • 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: 5170–5172

    PubMed  CAS  Google Scholar 

  • Akil H, Watson SJ, Young E, Lewis ME, Khachaturian H, Walker JM (1984) Endogenous opioids: biology and function. Annu Rev Neurosci 7: 223–255

    PubMed  CAS  Google Scholar 

  • 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: 287–300

    Google Scholar 

  • Angulo JA, Davis LG, Burkhart BA, Christoph GR (1986) Reduction of striatal dopaminergic neurotransmission elevates striatal pro-enkephalin mRNA. Eur J Pharmacol 130: 341–343

    PubMed  CAS  Google Scholar 

  • Baldino F, Chesselet MF, Lewis ME (1989) High resolution in situ hybridization histochemistry. Methods Enzymol 168: 761–777

    PubMed  CAS  Google Scholar 

  • Basbaum Al, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7: 309–234

    PubMed  CAS  Google Scholar 

  • 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: 43–48

    PubMed  CAS  Google Scholar 

  • 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: 1591–1595

    PubMed  CAS  Google Scholar 

  • Blum M, Roberts JL, Wardlaw SL (1989) Androgen regulation of proopiomelanocortin expression and peptide content in the basal hypothalamus. Endocrinology 124: 2283–2288

    PubMed  CAS  Google Scholar 

  • Bronstein DM, Przewlocki R, Akil H (1990) Effects of morphine treatment of proopiomelanocortin systems in rat brain. Brain Res 519: 102–111

    PubMed  CAS  Google Scholar 

  • 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: 733–7838

    PubMed  CAS  Google Scholar 

  • Cassell MD, Gray TS (1989) Morphology of peptide-immunoreactive neurons in the rat central nucleus of the amygdala. J Comp Neurol 281: 320–333

    PubMed  CAS  Google Scholar 

  • Chavkin C, James I, Goldstein A (1982) Dynorphin is a specific endogenous ligand of the kappa opioid receptor. Science 215: 413–415

    PubMed  CAS  Google Scholar 

  • Chesselet MF (1990) In situ hybridization histochemistry. CRC Press, Boca Raton

    Google Scholar 

  • 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: 320–322

    PubMed  CAS  Google Scholar 

  • Cho HJ, Basbaum Al (1988) Increased staining of immunoreactive dynorphin cell bodies in the deafferented spinal cord of the rat. Neurosci Lett 84: 125–130

    PubMed  CAS  Google Scholar 

  • 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: 2875–2881

    PubMed  CAS  Google Scholar 

  • 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: 1697–1702

    PubMed  CAS  Google Scholar 

  • Chung K, Briner RP, Carlton SM, Westlund KN (1989) Immunohistochemical localization of seven different peptides in the human spinal cord. J Comp Neurol 280: 158–170

    PubMed  CAS  Google Scholar 

  • 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: 6783–6887

    PubMed  CAS  Google Scholar 

  • Clouet DH, Ratner M (1970) Catecholamine biosynthesis in rats treated with morphine. Science 168: 854–856

    PubMed  CAS  Google Scholar 

  • 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: 663–666

    PubMed  CAS  Google Scholar 

  • 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: 79–81

    PubMed  CAS  Google Scholar 

  • 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: 49–64

    PubMed  CAS  Google Scholar 

  • 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: 1067–1080

    PubMed  Google Scholar 

  • Dores RM, Akil H, Watson SJ (1984) Strategies for studying opioid peptide regulation at the gene, message, and protein levels. Peptides 5 (Suppl 1): 9–17

    PubMed  CAS  Google Scholar 

  • Eberwine JH, Roberts JL (1984) Glucocorticoid regulation of proopiomelanocrotin gene transcription in the rat pituitary. J Biol Chem 259: 2166–2170

    PubMed  CAS  Google Scholar 

  • 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: 349–351

    PubMed  CAS  Google Scholar 

  • 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: 1769–1772

    Google Scholar 

  • Fremeau RT, Lundblad JR, Pritchett DB, Wilcox JN, Roberts JL (1986) Regulation of pro-opiomelanocortin gene transcription in individual cell nuclei. Science 234: 1265–1269

    PubMed  CAS  Google Scholar 

  • 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: 197–201

    PubMed  CAS  Google Scholar 

  • Gall C, Lauterborn J, Isackson P, White J (1990) Seizures, neuropeptide regulation,and mRNA expression in the hippocampus. Prog Brain Res 83: 371–390

    PubMed  CAS  Google Scholar 

  • 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 374–376

    Google Scholar 

  • 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: 6666–6670

    PubMed  CAS  Google Scholar 

  • 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: 161–167

    PubMed  CAS  Google Scholar 

  • 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: 1429–1432

    PubMed  CAS  Google Scholar 

  • 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: 1016–1031

    PubMed  CAS  Google Scholar 

  • Gubler U, Seeburg P, Hoffman BJ, Gage LP, Udenfriend S (1982) Molecular cloning establishes pro-enkephalin as precursor of enkephalin-containing peptides. Nature 295: 206–208

    PubMed  CAS  Google Scholar 

  • Gulya K (1990) The opioid system in neurologic and psychiatric disorders and in their experimental models. Pharmacol Ther 46: 395–428

    PubMed  CAS  Google Scholar 

  • Haber SN, Elde R (1982) The distribution of enkephalin immunoreactive fibers and minals in the monkey central nervous system. Neuroscience 7: 1049–1095

    PubMed  CAS  Google Scholar 

  • Haber SN, Watson SJ (1985) The comparative distribution of enkephalin, dynorphin and substance P in the human globus pallidus and basal forebrain. Neuroscience 14: 1011–1024

    PubMed  CAS  Google Scholar 

  • 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: 348

    Google Scholar 

  • 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: 159–184

    PubMed  CAS  Google Scholar 

  • Hauser KF, Osborne JG, Stiene MA, Melner MH (1990) Cellular localization of proenkephaline mRNA and enkephalin peptide products in cultured astrocytes. Brain Res 522: 347–353

    PubMed  CAS  Google Scholar 

  • 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: 115–128

    PubMed  CAS  Google Scholar 

  • Herkenham M (1987) Mismatches between neurotransmitter and receptor localizations in brain: observations and implications. Neuroscience 23: 1–38

    PubMed  CAS  Google Scholar 

  • Herz A, Millan MJ (1988) Endogenous opioid peptides in the descending control of nociceptive responses of spinal dorsal horn neurons. Prog Brain Res 77: 263–273

    PubMed  CAS  Google Scholar 

  • 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: 33–70

    PubMed  Google Scholar 

  • 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: 249–255

    PubMed  CAS  Google Scholar 

  • 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: 90–94

    PubMed  Google Scholar 

  • Höllt V, Haarmann I, Reimer S (1989) Opioid gene expression in rats after chronic morphine treatment. Adv Biosci 75: 711–714

    Google Scholar 

  • Hong JS, Yoshikawa K, Kanamatsu T, Sabol SL (1985) Modulation of striatal enkephalinergic neurons by antipsychotic drugs. Fed Proc 44: 1535–2539

    Google Scholar 

  • 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: 141–157

    PubMed  CAS  Google Scholar 

  • 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: 48–46

    CAS  Google Scholar 

  • 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: 183–186

    PubMed  CAS  Google Scholar 

  • 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: 279–281

    PubMed  CAS  Google Scholar 

  • 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: 577–579

    PubMed  CAS  Google Scholar 

  • Iadarola MJ, Douglas J, Civelli O, Naranjo JR (1986) Increased spinal cord dynorphin mRNA during peripheral inflammation. NIDA Res Monogr Ser 75: 406–409

    CAS  Google Scholar 

  • 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: 205–212

    PubMed  CAS  Google Scholar 

  • 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: 131–135

    PubMed  CAS  Google Scholar 

  • 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: 445–456

    PubMed  CAS  Google Scholar 

  • Illes P (1989) Modulation of transmitter and hormone release by multiple neuronal opioid receptors. Rev Physiol Biochem Pharmacol 112: 139–233

    PubMed  CAS  Google Scholar 

  • Ito M (1984) The cerebellum and neural control. Raven, New York

    Google Scholar 

  • Jackson A, Cooper SJ (1988) Observational analysis of the effects of kappa opioid agonists on open field behaviour in the rat. Psychopharmacology (Berl) 94: 248–253

    CAS  Google Scholar 

  • Jiang H-K, McGinty JF, Hong JS (1990) Differential modulation of striatonigral dynorphin and enkephalin by dopamine receptor subtypes. Brain Res 507: 57–64

    PubMed  CAS  Google Scholar 

  • 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: 207–212

    PubMed  CAS  Google Scholar 

  • 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: 245–249

    PubMed  CAS  Google Scholar 

  • 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: 871–878

    PubMed  CAS  Google Scholar 

  • 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: 433–438

    Google Scholar 

  • Khachaturian H, Watson SJ (1982) Some perspectives on monoamine-opioid peptide interactions in rat central nervous system. Brain Res Bull 9: 441–462

    PubMed  CAS  Google Scholar 

  • Khachaturian H, Watson SJ, Lewis ME, Coy DH, Goldstein A, Akil H (1982) Dynorphin peptide immunocytochemistry in the rat central nervous system. Peptides 3: 941–954

    PubMed  CAS  Google Scholar 

  • Khachaturian H, Lewis ME, Höllt V, Watson SJ (1983a) Telencephalic enkephalinergic systems in the rat brain. J Neurosci 3: 844–855

    PubMed  CAS  Google Scholar 

  • Khachaturian H, Lewis ME, Watson SJ (1983b) Enkephalin systems in diencephalon and brainstem of the rat. J Comp Neurol 220: 310–320

    PubMed  CAS  Google Scholar 

  • Khachaturian H, Lewis ME, Watson SJ (1983c) Colocalization of pro-enkephalin peptides in rat brain neurons. Brain Res 279: 369–373

    PubMed  CAS  Google Scholar 

  • Khachaturian H, Lewis ME, Haber SN, Akil H, Watson SJ (1984) Pro-opiomelanocortin peptide immunocytochemistry in rhesus monkey brain. Brain Res Bull 13: 785–800

    PubMed  CAS  Google Scholar 

  • 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): 155–166

    PubMed  CAS  Google Scholar 

  • Khachaturian H, Lewis ME, Schäfer M-KH, Watson SJ (1985b) Anatomy of CNS opioid systems. Trends Neurosci 8: 111–119

    CAS  Google Scholar 

  • 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 

  • 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: 1409–1411

    PubMed  CAS  Google Scholar 

  • 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 233–247

    Google Scholar 

  • 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: 6480–6483

    PubMed  CAS  Google Scholar 

  • 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: 394–402

    PubMed  CAS  Google Scholar 

  • 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: 47–54

    PubMed  CAS  Google Scholar 

  • Lewis JW, Canno JT, Chudler EH, Liebeskind JC (1981) Effects of naloxone and hypophysectomy on electroconvulsive shock-induced analgesia. Brain Res 208: 230–233

    PubMed  CAS  Google Scholar 

  • Lewis ME, Krause RG II, Roberts-Lewis JM (1988) Recent developments in the use of synthetic oligonucleotides for in situ hybridization histochemistry. Synapse 2: 308–316

    PubMed  CAS  Google Scholar 

  • Li CH, Chung D (1976) Isolation and structure of a triakontapeptide with opiate activity from camel pituitary glands. Proc Natl Acad Sci USA 73: 1145–1148

    PubMed  CAS  Google Scholar 

  • 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: 390–392

    PubMed  CAS  Google Scholar 

  • 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: 403–408

    CAS  Google Scholar 

  • Lightman SL, Young WS (1987) Changes in hypothalamic preproenkephalin A mRNA following stress and opiate withdrawal. Nature 328: 643–645

    PubMed  CAS  Google Scholar 

  • Loh HH, Smith AP (1990) Molecular characterization of opioid receptors. Annu Rev Pharmacol Toxicol 30: 123–147

    PubMed  CAS  Google Scholar 

  • Mains RE, Eipper EA, Ling N (1977) Common precursor to corticotropins and endorphins. Proc Natl Acad Sci USA 74: 3014–3018

    PubMed  CAS  Google Scholar 

  • Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ (1988) Anatomy of CNS opioid receptors. Trends Neurosci 11: 308–314

    PubMed  CAS  Google Scholar 

  • 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: 192–221

    PubMed  CAS  Google Scholar 

  • 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 136:405–407

    PubMed  CAS  Google Scholar 

  • Mayer DJ, Hayes RL (1975) Stimulation-produced analgesia: development of tolerance and cross-tolerance to morphine. Science 188: 941–943

    PubMed  CAS  Google Scholar 

  • Mayer DJ, Wolfle TL, Akil H, Carder B, Liebeskind JC (1971) Analgesia from electrical stimulation in the brainstem of the rat. Science 174: 1351–1354

    PubMed  CAS  Google Scholar 

  • McCabe JT, Desharnais RA, Pfaff DW (1989) Graphical and statistical approaches to data analysis for in situ hybridization. Methods Enzymol 168: 822–848

    PubMed  CAS  Google Scholar 

  • McDowell J, Kitchen I (1987) Development of opioid systems: peptides, receptors and pharmacology. Brain Res Rev 12: 397–421

    CAS  Google Scholar 

  • 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: 1104–1117

    PubMed  CAS  Google Scholar 

  • 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: 283–289

    CAS  Google Scholar 

  • 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: 791–796

    PubMed  CAS  Google Scholar 

  • Millan MJ (1990) Kappa-opioid receptors and analgesia. Trends Pharmacol Sci 11: 7076

    Google Scholar 

  • 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 245–260

    Google Scholar 

  • 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: 619–628

    Google Scholar 

  • Milner TA, Pickel VM, Reis DJ (1989) Ultrastructural basis for interactions between central opioids and catecholamines: I. Rostral ventrolateral medulla. J Neurosci 9: 2114–2130

    Google Scholar 

  • 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: 33–38

    PubMed  CAS  Google Scholar 

  • Moon SL (1984) Prenatal haloperidol alters striatal dopamine and opiate receptors. Brain Res 323: 109–113

    PubMed  CAS  Google Scholar 

  • Moon Edley S, Hall SL, Herkenham M, Pert CB (1982) Evolution of striatal opiate receptors. Brain Res 249: 184–188

    Google Scholar 

  • 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: 104–108

    PubMed  CAS  Google Scholar 

  • 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: 3226–3230

    CAS  Google Scholar 

  • 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: 525–532

    PubMed  CAS  Google Scholar 

  • 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: 9–18

    PubMed  CAS  Google Scholar 

  • 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: 439

    Google Scholar 

  • 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: 532–544

    PubMed  CAS  Google Scholar 

  • 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: 345–349

    PubMed  CAS  Google Scholar 

  • 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: 423–427

    PubMed  CAS  Google Scholar 

  • 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 64–110

    Google Scholar 

  • 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: 202–206

    PubMed  CAS  Google Scholar 

  • Olson GA, Olson RD, Kastin AJ (1989) Endogenous opiates: 1988. Peptides 10: 1253–1280

    PubMed  CAS  Google Scholar 

  • Pasternak GW (1988) Multiple morphine and enkephalin receptors and the relief of pain. JAMA 259: 1362–1367

    PubMed  CAS  Google Scholar 

  • 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 

  • 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: 2519–2535

    Google Scholar 

  • 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: 611–615

    PubMed  CAS  Google Scholar 

  • Polakiewicz RD, Rosen H (1990) Regulated expression of proenkephalin A during ontogenic development of mesenchymal derivative tissues. Mol Cell Biol 10: 736–742

    PubMed  CAS  Google Scholar 

  • Quirion R, Weiss AS (1983) Peptide E and other pro-enkephalin-derived peptides are kappa opiate receptor agonists. Peptides 4: 445–449

    CAS  Google Scholar 

  • Reis DJ, Hess P, Azmitia E (1970) Changes in enzymes subserving catecholamine metabolism in morphine tolerance and withdrawal in rat. Brain Res 20: 309–312

    PubMed  CAS  Google Scholar 

  • Richardson DE, Akil H (1977a) Pain reduction by electrical brain stimulation in man: 1. Acute administration in periaqueductal and periventricular sites. J Neurosurg 47: 184–194

    Google Scholar 

  • 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: 184–194

    Google Scholar 

  • 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: 5300–5304

    PubMed  CAS  Google Scholar 

  • 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: 33–41

    CAS  Google Scholar 

  • 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: 51–58

    PubMed  CAS  Google Scholar 

  • 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: 63–68

    PubMed  CAS  Google Scholar 

  • Rosen H, Behar O, Abramsky O, Ovadia H (1989) Regulated expression of proenkephalin A in normal lymphocytes. J Immunol 143: 3703–3707

    PubMed  CAS  Google Scholar 

  • Rougeot C, Charnay Y, Dray F, Dubois PM (1988) Chromatographic identification of Met- and Leu-enkephalin in the human fetal spinal cord. Peptides 9: 125–131

    PubMed  CAS  Google Scholar 

  • 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: 622–626

    PubMed  CAS  Google Scholar 

  • 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: 391–399

    PubMed  CAS  Google Scholar 

  • 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: 8–14

    PubMed  CAS  Google Scholar 

  • 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: 599–602

    Google Scholar 

  • 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: 444–448

    PubMed  Google Scholar 

  • 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: 1276

    Google Scholar 

  • 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 53–71

    Google Scholar 

  • Schwartzberg DG, Nakane PK (1983) ACTH-related peptide containing neurons within the medulla oblongata of the rat. Brain Res 276: 351–356

    PubMed  CAS  Google Scholar 

  • 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: 447–457

    Google Scholar 

  • 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: 110–116

    PubMed  CAS  Google Scholar 

  • 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: 2323–2327

    PubMed  CAS  Google Scholar 

  • Shinoda H, Marini AM, Cosi C, Schwartz JP (1989) Brain region and gene specificity of neuropeptide gene expression in cultured astrocytes. Science 245: 415–417

    PubMed  CAS  Google Scholar 

  • 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: 243–256

    PubMed  CAS  Google Scholar 

  • 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: 442–459

    PubMed  CAS  Google Scholar 

  • 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: 186–191

    PubMed  CAS  Google Scholar 

  • Smith CB, Villarreal JE, Bednarczyk JH, Sheldon MI (1970) Tolerance to morphine- induced increases in (11C) catecholamine synthesis in mouse brain. Science 170: 1106–1108

    PubMed  CAS  Google Scholar 

  • Smith EM, Morill AC, Meyer WJ, Blalock JE (1986) Corticotropin releasing factor induction of leucocyte-derived immunoreactive ACTH and endorphins. Nature 321: 881–882

    PubMed  CAS  Google Scholar 

  • 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: 1787–1795

    PubMed  CAS  Google Scholar 

  • Stefano GB (1989) Role of opioid neuropeptides in immunoregulation. Prog Neurobiol 33: 149–159

    PubMed  CAS  Google Scholar 

  • 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: 1–119

    PubMed  CAS  Google Scholar 

  • 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: 3841–3844

    PubMed  CAS  Google Scholar 

  • Thompson LA, Matsumoto RR, Hohmann AG, Walker JM (1990) Striatonigral prodynorphin: a model system for understanding opioid peptide function. Ann NY Acad Sci 579: 192–203

    PubMed  CAS  Google Scholar 

  • Topel H (1988) Beta-endorphin genetics in the etiology of alcoholism. Alcohol 5: 159–165

    PubMed  CAS  Google Scholar 

  • 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: 550–551

    Google Scholar 

  • 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: 28–35

    PubMed  CAS  Google Scholar 

  • 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: 195–205

    PubMed  CAS  Google Scholar 

  • Uhl G (1986) In situ hybridization in brain. Plenum, New York

    Google Scholar 

  • Valentino KL, Eberwine JH, Barchas JD (1987) In situ hybridization: applications to neurobiology. Oxford University Press, Oxford

    Google Scholar 

  • Vilijn MH, Vaysse PJ, Zukin RS, Kessler JA (1988) Expression of preproenkephalin mRNA by cultured astrocytes and neurons. Proc Natl Acad Sci USA 85: 6551–6555

    PubMed  CAS  Google Scholar 

  • Vincent SR, Hokfelt T, Christensson I, Terenius L (1982) Dynorphin immunoreactive neurons in the central nervous system of the rat. Neurosci Lett 33: 185–190

    PubMed  CAS  Google Scholar 

  • 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: 53–59

    PubMed  CAS  Google Scholar 

  • 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: 272–282

    PubMed  CAS  Google Scholar 

  • Watson SJ, Akil H (1980) Alpha-MSH in rat brain: occurrence within and outside brain beta-endorphin neurons. Brain Res 182: 217–223

    PubMed  CAS  Google Scholar 

  • Watson SJ, Akil H, Richard CW, Barchas JD (1978a) Evidence for two separate opiate peptide neuronal systems. Nature 275: 226–228

    PubMed  CAS  Google Scholar 

  • Watson SJ, Richard CW, Barchas JD (1978b) Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons. Science 200: 1180–1182

    PubMed  CAS  Google Scholar 

  • Watson SJ, Akil H, Ghazarossian VE, Goldstein A (1981) Dynorphin immunocytochemical localization in brain and peripheral nervous system. Proc Natl Acad Sci USA 78: 1260–1263

    PubMed  CAS  Google Scholar 

  • 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: 85–87

    PubMed  CAS  Google Scholar 

  • 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: 1134–1136

    PubMed  CAS  Google Scholar 

  • 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: 891–894

    PubMed  CAS  Google Scholar 

  • 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 3–33

    Google Scholar 

  • 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 225–241

    Google Scholar 

  • 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: 1125–1129

    PubMed  CAS  Google Scholar 

  • Weber E, Evans CJ, Barchas JD (1982) Predominance of the amino-terminal beta- peptide fragment of dynorphin in rat brain regions. Nature 299: 77–79

    PubMed  CAS  Google Scholar 

  • 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: 189–199

    PubMed  CAS  Google Scholar 

  • 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: 255–259

    PubMed  CAS  Google Scholar 

  • 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: 77–95

    PubMed  CAS  Google Scholar 

  • 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 

  • 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: 7099–7103

    PubMed  CAS  Google Scholar 

  • 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: 1760–1767

    PubMed  CAS  Google Scholar 

  • Wilcox JN, Roberts JL (1985) Estrogen decreases rat hypothalamic proopiomelanocortin messenger ribonucleic acid levels. Endocrinology 117: 2392–2396

    PubMed  CAS  Google Scholar 

  • 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: 11–19

    PubMed  CAS  Google Scholar 

  • 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: 175–183

    PubMed  CAS  Google Scholar 

  • 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 121:355–365

    PubMed  CAS  Google Scholar 

  • Young WS (1990) In situ hybridization histochemistry. In: Hokfelt T (ed) Handbook of chemical neuroanatomy, vol 7. Elsevier, Amsterdam, pp 481–512

    Google Scholar 

  • 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: 9827–9831

    PubMed  CAS  Google Scholar 

  • Zagon DS, Rhodes RE, McLaughlin PJ (1985) Distribution of enkephalin immuno- reactivity in germinativa cells of developing rat cerebellum. Science 227: 1049–1051

    PubMed  CAS  Google Scholar 

  • Zardetto-Smith AM, Moga MM, Magnuson DJ, Gray TS (1988) Lateral hypothalamic dynorphinergic efferents to the amygdala and brainstem in rat. Peptides 9: 1121–1127

    PubMed  CAS  Google Scholar 

  • 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: 772–775

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. H. Khachaturian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. K. H. Schaefer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. E. Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Abteilung Neuropharmakologie, Max-Planck-Institut für Psychiatrie, Am Klopferspitz 18, W-8033, Martinsried, Germany

    Albert Herz

  2. Mental Health Research Institute, School of Medicine, University of Michigan, 205 Zina Picher, 48109, Ann Arbor, MI, USA

    Huda Akil

  3. Medical Center, School of Medicine, New York University, 550 First Avenue, 10016, New York, NY, USA

    Eric J. Simon

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Khachaturian, H., Schaefer, M.K.H., Lewis, M.E. (1993). Anatomy and Function of the Endogenous Opioid Systems. In: Herz, A., Akil, H., Simon, E.J. (eds) Opioids. Handbook of Experimental Pharmacology, vol 104 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77460-7_20

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-77460-7_20

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-77462-1

  • Online ISBN: 978-3-642-77460-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation