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Neuropeptide-Dopamine Interactions: Focus on Neurotensin

  • Chapter
Dopaminergic Systems and their Regulation

Abstract

The emphasis of this chapter is on the mechanisms and functional significance of the interaction of neuropeptides with the putative neurotransmitter dopamine in the central nervous system (CNS). Accumulating evidence supports the contention that these interactions are of physiological importance and have added a novel dimension to our concepts of the pathophysiology of psychiatric disorders and the mechanisms of psychotropic drug action. Primary emphasis has been placed on findings from our laboratories and those of others concerning interactions between the tridecapeptide neurotensin (NT) and dopamine neurons. Where appropriate, the influence of other neuropeptides on dopamine mechanisms are discussed. We (Nemeroff et al., 1982a, 1983a, 1984) and others (Goedert, 1984) have previously reviewed the neuropharmacological, neuroanatomical and neurochemical literature supporting a functional interaction between NT-containing and dopamine-containing cells in the CNS and the interested reader is referred to these articles for a more comprehensive review than is intended here. The major objective of this chapter is to integrate recent data concerning the molecular basis of NT-dopamine interactions into the developing concept of the functional significance of such interactions.

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References

  • Agnati, L.F., Fuxe, K., Benfenati, F., and Battistini, N. (1983). Neurotensin In Vitro Markedly Reduces the Affinity in Subcortical Limbic 3H-N-Propylnorapomorphine Binding Sites. Acta Physiol. Scand., 119:459–461.

    CAS  Google Scholar 

  • Agnati, L.F., Fuxe, K., Battistini, N., and Benfenati, F. (1984). Aging Brain and Dopamine Receptors: Abnormal Regulation by CCK-8 of 3H-Spiperone Labeled Dopamine Receptors in Striatal Membranes. Acta. Physiol. Scand. 120:465–467.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, C.M., Bissette, G., Nemeroff, C.B., and Kilts, C.D. (1984). Microtopographic Distribution of Neurotensin and Catecholamine Concentrations at the Level of Individual Rat Brain Nuclei. Soc. Neurosci. Abs. 10:437.

    Google Scholar 

  • Andrade, R. and Aghajanian, G.K. (1981). Neurotensin Selectively Activates Dopamine Neurons in the Substantia Nigra. Soc. Neurosci. Abs. 7:573.

    Google Scholar 

  • Baldessarini, R.J. and Tarsy, D. (1980). Pathophysiologic basis of tardive dyskinesia. Adv. Biochem. Psychopharmacol. 24:451–455.

    PubMed  CAS  Google Scholar 

  • Beal, M.F. and Martin, J.B. (1984). Effects of Neuroleptic Drugs on Brain Somatostatin-Like-Immunoreactivity. Neurosci. Let. 47:125–130.

    Article  CAS  Google Scholar 

  • Bissette, G. and Nemeroff, C.B. (1984). Do Neuropeptide Systems Mediate Some of the Effects of Antipsychotic Drugs? In Endocoids. (eds. H. Lal, F. LaBella, and J. Lane). Alan R. Liss, Publishers, New York.

    Google Scholar 

  • Bissette, G., Nemeroff, C.B., Decker, M.W., Kizer, J.S., Agid, Y., and Javoy-Agid, F. (1984a). Alterations in Regional Brain Concentrations of Neurotensin and Bombesin in Parkinson’s Disease. Ann. Neurol. (in press).

    Google Scholar 

  • Bissette, G., Richardson, C., Kizer, J.S., and Nemeroff, C.B. (1984b). Ontogeny of Brain Neurotensin in the Rat: A Radioimmunoassay Study. J. Neurochem., 43:283–287.

    Article  PubMed  CAS  Google Scholar 

  • Bunney, B.S. and Aghajanian, G.R. (1975). Evidence for Drug Actions on Both Pre- and Postsynaptic Receptors in the CNS. In Pre- and Post-Synaptic Receptors. (eds. E. Usdin and W.E. Bunney) Marcel Dekker, New York.

    Google Scholar 

  • Carlsson, A. (1978). Mechanism of Action of Neuroleptic Drugs. In Psychopharmacology: A Generation of Progress. (eds. M.A. Lipton, A. Dimascio, and K.F. Killam) Raven Press, New York.

    Google Scholar 

  • Chou, J., Tang, J., Yang, H-Y.T., and Costa, E. (1983). Increase of Striatal Met5-Enkephalin-Arg-Phe7 (YGGFMRF) Content Elicited by Long-Term Treatment with Haloperidol. J. Pharm. Exp. Ther. 229:171–174.

    Google Scholar 

  • Dichiara, G., Porceddu, M.L., Spano, P.F., and Gessa, G.L. (1977). Haloperidol Increases and Apomorphine Decreases Striatal Dopamine Metabolism After Destruction of Striatal Dopamine-Sensitive Adenylate Cyclase by Kainic Acid. Brain Res. 130:374–382.

    Article  CAS  Google Scholar 

  • Emson, P.C., Goedert, M., Williams, B., Ninkovic, M., and Hunt, S.P. (1982). Neurotensin: Regional Distribution, Characterization, and Inactivation. In Neurotensin. a Brain and Gastrointestinal Peptide. (eds. C.B. Nemeroff and A.J. Prange, Jr.) N. Y. Academy of Sciences, New York.

    Google Scholar 

  • Ervin, G.M., Birkemo, L.S., Nemeroff, C.B. and Prange, A.J. (1981). Neurotensin Blocks Certain Amphetamine-induced Behaviors. Nature 291:73–76.

    Article  PubMed  CAS  Google Scholar 

  • Frey, P. (1983). Cholecystokinin Octapeptide Levels in Rat Brain are Changed After Subchronic Neuroleptic TReatment. Eur. J. Pharmacol. 95:87–92.

    Article  PubMed  CAS  Google Scholar 

  • Fuxe, K., Agnati, L.F., Benfenati, F., Celani, M., Zini, I., Zoli, M., and Mutt, V. (1983). Evidence for the Existence of Receptor-Receptor Interactions in the Central Nervous System. Studies on the Regulation of Monoamine Receptors by Neuropeptides. J. Neural Transmission. Suppl. 19:165–179.

    Google Scholar 

  • Garcia-Sevilla, J.A., Magnusson, T., Carlsson, A., Leban, J., and Folkgrs, K. (1978). Neurotensin and Its Amide Analogue [Gln4]-Neurotensin: Effects on Brain Monoamine Turnover. Naunyn-Schmiedeberg’s Arch. Pharmacol. 305:213–218.

    CAS  Google Scholar 

  • Gerlach, J., Thorse, K., and Fog, R. (1975). Extrapyramidal Reactions and Amine Metabolites in Cerebrospinal Fluid During Haloperidol and Clozapine Treatment of Schizophrenic Patients. Psychopharmacologia (Berl.) 40:341–350.

    Article  CAS  Google Scholar 

  • Gilbert, J.A., McKinney, M., and Richelson, E. (1984). Neurotensin Stimulates Cyclic GMP Fromation in Neuroblastoma Clone N1E-115 and Rat Cerebellum. Soc. Neurosci. Abs. 10:378.

    Google Scholar 

  • Gilbert, J.A. and Richelson, E. (1984). Neurotensin Stimulates Formation of Cyclic GMP in Murine Neuroblastoma Clone N1E-115. Eur. J. Pharmacol., 99:245–246.

    Article  PubMed  CAS  Google Scholar 

  • Glimcher, P.W., Margolin, D.H., Giovino, A.A., and Hoebel, B.G. (1984). Neurotensin: A New ‘Reward Peptide’. Brain Res. 291:119–124.

    Article  PubMed  CAS  Google Scholar 

  • Goedert, M. (1984). Neurotensin — a status report. Trends in Neurosci. 7:3–5.

    Article  CAS  Google Scholar 

  • Goedert, M., Pittaway, K., and Emson, P.C. (1984a). Neurotensin Receptors in the Rat Striatum: lesion studies. Brain Res. 299:164–168.

    Article  PubMed  CAS  Google Scholar 

  • Goedert, M., Pittaway, K. Williams, B.J., and Emson, P.C. (1984b). Specific Binding of Tritiated Neurotensin to Rat Brain Membranes: Characterization and Regional Distribution. Brain Res. 304:71–81.

    Article  PubMed  CAS  Google Scholar 

  • Goedert, M., Mantyh, P.W., Emson, P.C., and Hunt, S.P. (1984c). Inverse Relationship Between Neurotensin Receptors and Neurotensin-line Immunoreactivity in Cat Striatum. Nature, 307:543–546.

    Article  PubMed  CAS  Google Scholar 

  • Govoni, S., Hong, J.S., Yang, Y.-H.T., and Costa, E. (1980). Increase of Neurotensin Content Elicited by Neuroleptics in Nucleus Accumbens. J. Pharm. Exp. Ther. 215:413–417.

    CAS  Google Scholar 

  • Haubrich, D.R., Martin, G.E., Martin, E., Pflueger, A.B., and Williams, M. (1982). Neurotensin Effects on Brain Dopaminergic Systems. Brain Res. 231:216–221.

    Article  PubMed  CAS  Google Scholar 

  • Henry, J.L. (1982). Electrophysiological Studies on the Neuroactive Properties of Neurotensin. In Neurotensin. a Brain and Gastrointestinal Peptide. (eds. C.B. Nemeroff and A.J. Prange, Jr.) N. Y. Academy of Sciences, New York.

    Google Scholar 

  • Hernandez, D.E., Richardson, C.M., Nemeroff, C.B., Orlando, R.C., St-Pierre, S., Rioux, F., and Prange, A.J. (1984). Evidence for Biological Activity of Two N-Terminal Fragments of Neurotensin, Neurotensin1–8 and Neurotensin1–10. Brain Res. 301:153–156.

    Article  PubMed  CAS  Google Scholar 

  • Hokfelt, T., Everitt, B.J., Theodorsson-Norheim, E., and Goldstein, M. (1984). Occurrence of Neurotensin-like Immunoreactivity in Subpopulations of Hypothalamic, Mesencephalic, and Medullary Catecholamine Neurons. J. Comp. Neurol. 222: 543–559.

    Article  PubMed  CAS  Google Scholar 

  • Hong, J.S., Yang, Y.-H.T., Fratta, W., and Costa, E. (1978). Rat Striatal Methionine-Enkephalin Content After Chronic Treatment with Cataleptogenic and Noncataleptogenic Antischizophrenic Drugs. J. Pharm. Exp. Ther. 205:141–147.

    CAS  Google Scholar 

  • Hong, J.-S., Tilson, H.A., and Yoshikawa, R. (1982). Effects of Lithium and Haloperidol Administration on the Rat Brain Levels of Substance P. J. Pharm. Exp. Ther. 224:590–593.

    Google Scholar 

  • Ibata, Y., Okamura, F.H., Rawakami, T., Tanaka, M., Obata, H.L., Tsuto, O.T., Terubayashi, H., Yanaibara, C., and Yanaihara, N. (1983). Coexistence of Dopamine and Neurotensin in Hypothalamic Arcuate and Periventricular Neurons. Brain Res. 269:177–179.

    Article  PubMed  CAS  Google Scholar 

  • Iversen, L.L., Iversen, S.D., Bloom, F., Douglas, C., Brown, M., and Vale, W. (1978). Calcium-Dependent Release of Somatostatin and Neurotensin from Rat Brain In Vitro. Nature 273:161.

    Article  PubMed  CAS  Google Scholar 

  • Jennes, L., Stumpf, W.E., and Kalivas, P.W. (1982). Neurotensin: Topographical Distribution in Rat Brain by Immunohistochemistry. J. Comp. Neurol. 210:211–224.

    Article  PubMed  CAS  Google Scholar 

  • Jolicoeur, F.B. and Barbeau, A. (1982). Pharmacological Evidence for a Heterogeneity of Receptors Underlying Various Central and Peripheral Effects of Neurotensin. In Neurotensin. a Brain and Gastrointestinal Peptide. (eds. C.B. Nemeroff and A. J. Prange, Jr.) N. Y. Academy of Sciences, New York.

    Google Scholar 

  • Jolicoeur, F.B., De Michele, G., and Barbeau, A. (1983). Neurotensin Affects Hyperactivity but not Stereotypy Induced by Pre and Post Synaptic Dopaminergic Stimulation. Neurosci. Biobehav. Rev. 7:385–390.

    Article  PubMed  CAS  Google Scholar 

  • Kalivas, P.W., Nemeroff, C.B., and Prange, A.J. (1981). Increase in Spontaneous Motor Activity Following Infusion of Neurotensin into the Ventral Tegmental Area. Brain Res. 229:525–529.

    Article  PubMed  CAS  Google Scholar 

  • Kalivas, P.W., Nemeroff, C.B., and Prange, A.J., Jr. (1982a). Neuroanatomical Site Specific Modulation of Spontaneous Motor Activity by Neurotensin. Eur. J. Pharm. 78:471–474.

    Article  CAS  Google Scholar 

  • Kalivas, P.W., Nemeroff, C.B. and Prange, A.J. (1982b) Neuroanatomical Sites of Action of Neurotensin. In Neurotensin. a Brain and Gastrointestinal Peptide. (eds. C.B. Nemeroff and A. J. Prange, Jr.) N. Y. Academy of Sciences, New York.

    Google Scholar 

  • Kalivas, P.W., Burgess, S.K., Nemeroff, C.B., and Prange, A.J., Jr. (1983). Behavioral and Neurochemical Effects of Neurotensin Microinjection into the Ventral Tegmental Area of the Rat. Neurosci. 8:495–505.

    Article  CAS  Google Scholar 

  • Kalivas, P.W. (1984). Neurotenain in the Ventromedial Mesencephalon of the Rat: Anatomical and Functional Considerations. J. Comp. Neurol. 226:495–507.

    Article  PubMed  CAS  Google Scholar 

  • Kalivas, P.W., Nemeroff, C.B., and Prange, A.J., Jr. (1984). Neurotensin Microinjection into the Nucleus Accumbens Antagonizes Dopamine-Induced Increase in Locomotion and Rearing. Neurosci. 11:919–930.

    Article  CAS  Google Scholar 

  • Kebabian, J.W. and Calne, D.B. (1979). Multiple Receptors for Dopamine. Nature 277:93–96.

    Article  PubMed  CAS  Google Scholar 

  • Kilts, C.D., Gooch, M.D. and Knopes, R.D. (1984). Quantitation of Plasma Catecholamines by On-Line Trace Enrichment High Performance Liquid Chromatography with Electrochemical Detection. J. Neurosci. Methods, (in press).

    Google Scholar 

  • Kobayashi, R.M., Brown, M., and Vale, W. (1977). Regional Distribution of Neurotensin and Somatostatin in Rat Brain. Brain Res. 126:584–588.

    Article  PubMed  CAS  Google Scholar 

  • Lindvall, O. and Bjorklund, A. (1983). Dopamine- and Norepinephrine-Containing Neuron Systems: Their Anatomy in the Rat Brain. In Chemical Neuroanatomy. (ed. by P. Emson). Raven Press, New York.

    Google Scholar 

  • Loosen, P.T., Nemeroff, C.B., Bissette, G., Prange, A.J., Jr., Burnett, G.B., and Lipton, M.A. (1978). Neurotensin-induced Hypothermia in the Rat: Structure-activity Studies. Neuropharmacology 17:109–113.

    Article  PubMed  CAS  Google Scholar 

  • Manberg, P.J., Youngblood, W.W., Nemeroff, C.B., Rossor, M., Iversen, L.L., Prange, A.J., Jr., and Kizer, J.S. (1982). Regional Distribution of Neurotensin in Human Brain. J. Neurochem. 38:1777–1780.

    Article  PubMed  CAS  Google Scholar 

  • Marwaha, J., Hoffer, B., and Freedman, R. (1980). Electrophysiological Actions of Neurotensin in Rat Cerebellum. Reg. Peptides 1:115–125.

    Article  CAS  Google Scholar 

  • McCarthy, P.S., Waller, R.J., Yajima, H., Mitagawa, K., and Woodruff, G.H. (1979). The Action of Neurotensin on Neurons in the Nucleus Accumbens and Cerebellum of the Rat. Gen. Pharmacol. 10:331–333.

    Article  PubMed  CAS  Google Scholar 

  • Meltzer, H.Y. and Stahl, S.M. (1976). The dopamine hypothesis of schizophrenia: A review. Schizophrenia Bull. 2:19–76.

    Article  CAS  Google Scholar 

  • Miletic, V. and Randic, M. (1979). Neurotensin Excites Cat Spinal Neurones Located in Laminae I–III. Brain Res. 169:600–604.

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff, C.B., Hernandez, D.E., Luttinger, D., Kalivas, P., and Prange, A.J., Jr. (1982a). Interactions of Neurotensin with Brain Dopamine Systems. In Neurotensin. a Brain and Gastrointestinal Peptide. (eds. C.B. Nemeroff and A. J. Prange, Jr.) N. Y. Academy of Sciences, New York.

    Google Scholar 

  • Nemeroff, C.B., Hernandez, D.E., Orlando, R.C., and Prange, A.J., Jr. (1982b). Cytoprotective Effect of Centrally Administered Neurotensin on Stress-Induced Gastric Ulcers. Amer. J. Physiol. 242:342–346.

    Google Scholar 

  • Nemeroff, C.B., Luttinger, D., Hernandez, D.E., Mailman, R.B., Mason, G.A., Davis, S.D., Widerlov, E., Frye, G.D., Kilts, C.D., Beaumont, K., Breese, G.R., and Prange, A.J., Jr. (1983a). Interactions of Neurotensin with Brain Dopamine Systems: Biochemical and Behavioral Studies. J. Pharmacol. Exp. Ther. 225:337–345.

    PubMed  CAS  Google Scholar 

  • Nemeroff, C.B., Youngblood, W., Manberg, P.J., Prange, A.J., Jr., and Kizer, J.S. (1983b). Regional Brain Concentrations of Neuropeptides in Huntington’s Chorea and Schizophrenia. Science 221:972–975.

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff, C.B., Kalivas, P.W., and Prange, A.J., Jr. (1984). Interaction of Neurotensin and Dopamine in Limbic Structures. (eds. E. Usdin, A. Carlsson, A. Dahlstrom and J. Engel) Catecholamines: Neuropharmacolosty and Central Nervous System — Theoretical Aspects. Alan R. Liss, New York.

    Google Scholar 

  • Okuma, Y., Fukuda, Y., and Osumi, Y. (1983). Neurotensin Potentiates the Potassium-Induced Release of Endogenous Dopamine From Rat Striatal Slices. Eur. J. Pharmacol. 93:27–33.

    Article  PubMed  CAS  Google Scholar 

  • Palacios, J.M. and Kuhar, M.J. (1981). Neurotensin Receptors are Located on Dopamine-containing Neurones in Rat Midbrain. Nature 294:587–589.

    Article  PubMed  CAS  Google Scholar 

  • Palkovits, M. (1973). Isolated Removal of Hypothalamic or Other Brain Nuclei of the Rat. Brain Res. 59:449–450.

    Article  PubMed  CAS  Google Scholar 

  • Phillis, J.W. and Kirkpatrick, J.R. (1980). The Actions of Motilin, Leutinizing Hormone Releasing Hormone, Cholecystokinin, Somatostatin, Vasoactive Intestinal Peptide and Other Peptides on Rat Cerebral Cortical Neurons. Can. J. Physiol. Pharmacol. 58:612–623.

    Article  PubMed  CAS  Google Scholar 

  • de Quidt, M. and Emson, P.C. (1983). Neurotensin Facilitates Dopamine Release In Vitro From Rat Striatal Slices. Brain Res. 274:376–380.

    Article  PubMed  Google Scholar 

  • Quirion, R., Everist, H.D., and Pert, A. (1982). Nigrostriatal Dopamine Terminals Bear Neurotensin Receptors but the Mesolimbic Do Not. Soc. Neurosci. Abs. 8:582.

    Google Scholar 

  • Reches, A., Burke, R.E., Jiang, D., Wagner, H.R., and Fahn, S. (1982). The Effect of Neurotensin on Dopaminergic Neurons in Rat Brain. In Neurotensin, a Brain and Gastrointestinal Peptide. (eds. C.B. Nemeroff and A.J. Prange, Jr.) N. Y. Academy of Sciences, New York.

    Google Scholar 

  • Sawada, S., Takada, S., and Yamamoto, C. (1980). Electrical Activity Recorded from Thin Sections of the Bed Nucleus of the Stria Terminalis, and the Effects of Neurotensin. Brain Res. 188:578–581.

    Article  PubMed  CAS  Google Scholar 

  • Seeman, P. (1980). Dopamine Receptors. Pharmacol. Rev. 3:229–313.

    Google Scholar 

  • Snyder, S.H. (1972). Catecholamines in the Brain as mediators of Amphetamine psychosis. Arch. Gen. Psychiatry 27: 169–179.

    Article  PubMed  CAS  Google Scholar 

  • Stevens, J.R. (1973). An anatomy of Schizophrenia? Arch. Gen. Psychiatry 29: 177–189.

    Article  CAS  Google Scholar 

  • Uhl, G.R. and Kuhar, M.J. (1984). Chronic Neuroleptic Treatment Enhances Neurotensin Receptor Binding in Human and Rat Substantia Nigra. Nature 309:350–352.

    Article  PubMed  CAS  Google Scholar 

  • Walters, J.R. and Roth, R.H. (1976). Dopaminergic Neurons: An In Vivo System for Measuring Drug Interactions with Presynaptic Receptors. Naunyn-Schmiedeberg’s Arch. Pharmacol. 296:5–14.

    CAS  Google Scholar 

  • Widerlov, E., Kilts, C.D., Mailman, R.B., Nemeroff, C.B., Mc Cown, T.J., Prange, A.J., Jr., and Breese, G.R. (1982a). Increase in Dopamine Metabolites in Rat Brain by Neurotensin. J. Pharmacol. Exp. Ther. 222:1–6.

    Google Scholar 

  • Widerlov, E., Lindstrom, L. H., Besev, G., Manberg, P.J., Nemeroff, C.B., Breese, G.R., Kizer, J.S., and Prange, A.J., Jr. (1982b). Subnormal CSF Levels of Neurotensin in a Subgroup of Schizophrenic Patients: Normalization after Neuroleptic Treatment. Am. J. Psychiatr. 139:1122–1126.

    Article  PubMed  CAS  Google Scholar 

  • Young, W.S., III, Uhl, G.R., and Kuhar, M.J. (1978). Iontophoresis of Neurotensin in the Area of the Locus Coeruleus. Brain Res. 150:431–435.

    Article  PubMed  CAS  Google Scholar 

  • Young, W.S., III and Kuhar, M.J. (1979). Neurotensin Receptors: Autoradiographic Localization in Rat CNS. Eur. J. Pharmacol. 59:161–163.

    Article  PubMed  Google Scholar 

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Authors
  1. C. D. Kilts
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  2. G. Bissette
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  3. S. T. Cain
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  4. K. M. Skoog
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  5. C. B. Nemeroff
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Editors and Affiliations

  1. Merck Sharp and Dohme Research Laboratories, Harlow, Essex, UK

    G. N. Woodruff (Director of Pharmacology) (Director of Pharmacology)

  2. Department of Physiology and Pharmacology, University of Southampton, UK

    J. A. Poat  & P. J. Roberts  & 

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Kilts, C.D., Bissette, G., Cain, S.T., Skoog, K.M., Nemeroff, C.B. (1986). Neuropeptide-Dopamine Interactions: Focus on Neurotensin. In: Woodruff, G.N., Poat, J.A., Roberts, P.J. (eds) Dopaminergic Systems and their Regulation. Satellite Symposia of the IUPHAR 9th International Congress of Pharmacology. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-07431-0_15

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  • DOI: https://doi.org/10.1007/978-1-349-07431-0_15

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