Neuropeptides: Animal behaviour and human psychopathology

  • David de Wied
  • Jan M. van Ree
Article

Summary

Animal studies have demonstrated that neuropeptides modulate nervous system functions. It has been postulated that disturbances in neuropeptide systems may be aetiological factors in psychiatric and neurological disorders. Neuropeptides related to ACTH/MSH, including ORG 2766, increase motivation and attention and facilitate recovery processes after nerve damage. These peptides may be effective during the early stage of dementia. Vasopressin and related peptides improve memory processes in animals and humans. In addition, these peptides influence social behaviour, mood and addictive behaviour. The non-opioid γ-type endorphins have neurolepticlike activities in animals and antipsychotic effects in a category of schizophrenic patients. Peptides related to CCK have also been found to be effective in these patients. Some neuropeptides, e.g. TRH and PLG, have been reported to exert antidepressant effects. Further research may eventually produce neuropeptides with therapeutic action in psychiatric and neurological diseases.

Key words

Neuropeptides ACTH Vasopressin γ-type-Endorphins TRH Aging Memory Schizophrenia Affective disorders 

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References

  1. Azorin JM, Charbaut J, Granier F, Huber JP, Metzger JY, Richou H, Van Amerongen P, Blum A, Dufour H (1986) Des-enkephalin-gamma-endorphin in exacerbation of chronic schizophrenia: a double-blind, placebo-controlled study. Abstracts Symp Neuropeptides and Brain Function, May 1986, Utrecht, The Netherlands, p 103 P52Google Scholar
  2. Bloom DM, Nair NPV, Schwartz G (1983) CCK-8 in the treatment of chronic schizophrenia. Psychopharmacol Bull 19:361–363Google Scholar
  3. Bourgeois M, Laforge E, Muyard J, Blayac J, Lemoine J (1980) Endorphins et schizophrénies. Ann Med Psychol 138:1112–1119Google Scholar
  4. Bovenberg RAL, Burbach JPH, Wiegant VHM, Veeneman GH, Van Boom JH, Baas PD, Jansz HS, De Wied D (1986) γ-Endorphin and schizophrenia: amino acid composition of γ-endorphin and nucleotide sequence of γ-endorphin cDNA from pituitary glands of schizophrenic patients. Brain Res 376:29–37Google Scholar
  5. Brown MR, Fisher LA, Spiess J, Rivier C, Rivier J, Vale W (1982) Corticotropin-releasing factor: action on the sympathetic nervous system and metabolism. Endocrinology 111:928–931Google Scholar
  6. Burbach JPH (1986) Action of proteolytic enzymes on lipotropins and endorphins: biosynthesis, biotransformation and fate. In: De Wied C, Gispen WH, Van Wimersma Greidanus TjB (eds) Neuropeptides and behavior, vol 1. Pergamon Press, Oxford, pp 43–76Google Scholar
  7. Bijlsma WA, Schotman P, Jennekens FGI, Gispen WH, De Wied D (1983) The enhanced recovery of sensorimotor function in rats is related to the melanotropic moiety of ACTH/MSH neuropeptides. Eur J Pharmacol 92:231–236Google Scholar
  8. Casey DE, Korsgaard S, Gerlach J, Jørgensen A, Simmelsgaard H (1981) Effect of Des-Tyrosine-γ-endorphin in tardive dyskinesia. Arch Gen Psychiatry 38:158–160Google Scholar
  9. Chazot G, Claustrat B, Brun J, Olivier M (1985) Rapid antidepressant activity of destyr gamma endorphin: correlation with urinary melatonin. Biol Psychiatry 20:1026–1030Google Scholar
  10. Claas FHJ, Castelli-Visser R, De Jongh BM, Van Rood JJ, Verhoeven WMA, Van Ree JM, De Wied D (1984) Interaction between des-Tyrl-γ-endorphins and HLA class I molecules: clinical relevance for the treatment of schizophrenia? In: Medawar P, Lehner T (eds) Major histocompatibility system. Blackwell, Oxford, pp 106–113Google Scholar
  11. Davis TP, Schoemaker H, Culling AJ (1984) Centrally acting drugs alter in vitro β-endorphin processing in the rat. Eur J Pharmacol 100:249–251Google Scholar
  12. De Wied D (1978) Psychopathology as a neuropeptide dysfunction. In: Van Ree JM, Terenius L (eds) Characteristics and function of opioids. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 113–122Google Scholar
  13. De Wied D (1984) Neurohypophyseal hormone influences on learning and memory processes. In: Lynch G, McGaugh JL, Weinberger NM (eds) Neurobiology of learning and memory. Guildford Press, New York, pp 289–321Google Scholar
  14. De Wied D, Jolles J (1982) Neuropeptides derived from proopiocortin: behavioral, physiological and neurochemical effects. Physiol Rev 62:976–1059Google Scholar
  15. Eipper BA, Mains RE (1980) Structure and biosynthesis of pro-adrenocorticotropin/endorphin and related peptides. Endocr Rev 1:1–27Google Scholar
  16. Emrich HM, Zaudig M, Von Zerssen D, Kissling W, Dirlich G, Herz A (1981) Action of (des-Tyr1)-γ-endorphin in schizophrenia. In: Imrich HM (ed) Modern problems in pharmacopsychiatry, 17. The role of endorphins in neuropsychiatry. Karger, Basel, pp 279–286Google Scholar
  17. Fink M, Papakostas Y, Lee J, Meehan T, Johnson L (1981) Clinical trials with des-tyr-gamma-endorphin (GK-78). In: Perris C, Struwe G, Jansson B (eds) Biological psychiatry. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 398–401Google Scholar
  18. Fraenkel HM, Van Beek-Verbeek G, Fabriek AJ, Van Ree JM (1983) Desglycinamide9-arginine8-vasopressin and ambulant methadone-detoxification of heroin addicts. Alcohol Alcoholism 18:331–335Google Scholar
  19. Gaffori O, Van Ree JM (1985) β-Endorphin-(10–16) antagonizes behavioral responses elicited by melatonin following injection into the nucleus accumbens of rats. Life Sci 37:357–364Google Scholar
  20. Gaillard AWK (1981) ACTH analogs and human performance. In: Martinez JL, Jensen RA, Messing RB, Rigter H, McGaugh J (eds) Endogenous peptides and learning and memory. Academic Press, New York, pp 181–196Google Scholar
  21. Gispen WH, Isaacson RL (1986) Excessive grooming in response to ACTH. In: De Wied D, Gispen WH, Van Wimersma Greidanus TjB (eds) Neuropeptides and behavior, vol 1. Pergamon, Oxford, pp 272–312Google Scholar
  22. Hammonds RG Jr, Nicolas P, Li CH (1984) β-Endorphin(1–27) is an antagonist of β-endorphin analgesia. Proc Natl Acad Sci USA 81:1389–1390Google Scholar
  23. Hommer DW, Pickar D, Roy A, Ninan P, Boronow J, Paul SM (1984) The effects of ceruletide in schizophrenia. Arch Gen Psychiatary 41:617–619Google Scholar
  24. Itoh H, Tanoue S, Yagi G, Tateyama M, Kamisada M, Fujii Y, Takamiya M, Nakajima S (1982) Clinical study on the psychotropic effects of caerulein — an open clinical trial in chronic schizophrenic patients. Keio J Med 31:71–95Google Scholar
  25. Kissling W, Möller HJ, Bürk F, Kraemer S (1984) Multicenter double-blind comparison between des-enkephalin-γ-endorphin (DEγE, Org 5878) and haloperidol concerning the efficacy and safety in the treatment of schizophrenia. Abstracts 14th CINP Congress, Florence, Italy, p 146Google Scholar
  26. Korsgaard S, Casey DE, Gerlach J (1982) High dose destyrosine-γ-endorphin in ardive dyskinesia. Psychopharmacology 78:285–286Google Scholar
  27. Kragh-Sørensen P, Lolk A (1987) Neuropeptides and dementia. Prog Brain Res 72:269–277Google Scholar
  28. Laczi F, László FA, Kovács GL, Telegdy G, Szász A, Szilárd J, Van Ree JM, De Wied D (1987) Differential effect of desglycinamide9-(Arg8)-vasopressin on cognitive functions of diabetes insipidus and alcoholic patients. Acta Endocrinol 115:393–398Google Scholar
  29. Legros JJ, Lancranjan I (1984) Vasopressin in neuropsychiatric disorders. In: Nandkmar SS, Donald AG (eds) Psychoneuroendocrine dysfunction. Plenum, New York, pp 255–278Google Scholar
  30. Lotstra F, Verbanck P, Mendlewicz J, Vanderhaegen JJ (1984) No evidence of antipsychotic effect of caerulein in schizophrenic patients free of neuroleptics: a double-blind crossover study. Biol Psychiatry 19:877–882Google Scholar
  31. Manchanda R, Hirsch SR (1981) (Des-Tyr1)-γ-endorphin in the treatment of schizophrenia. Psychol Med 11:401–404Google Scholar
  32. Mattes JA, Hom W, Rochford JM, Orlosky M (1985) Ceruletide for schizophrenia: a double-blind study. Biol Psychiatry 20:533–538Google Scholar
  33. Meltzer HY, Busch DA, Tricou BJ, Robertson A (1982a) Effect of (Des-Tyr)-gamma-endorphin in schizophrenia. Psychiatry Res 6:313–326Google Scholar
  34. Meltzer HY, Busch DA, Lee J, Papacostas Y (1982b) Effect of Des-Tyr-γ-endorphin in schizophrenia. Psychopharmacol Bull 18:44–47Google Scholar
  35. Moroji T, Watanabe N, Aoki N, Itoh S (1982a) Antipsychotic effects of ceruletide (caerulein) on chronic schizophrenia. Arch Gen Psychiatry 39:485Google Scholar
  36. Moroji T, Watanabe N, Aoki N, Itoh S (1982b) Antipsychotic effects of caerulein, a decapeptide chemically related to cholecystokinin octapeptide, on schizophrenia. Int Pharmacopsychiatr 17:255–273Google Scholar
  37. Moss RL, Foreman MM (1976) Potentiation of lordosis behavior by intrahypothalamic infusion of synthetic luteinizing hormone-releasing hormone. Neuroendocrinology 20:176–181Google Scholar
  38. Nair NPV, Bloom DM, Nestoros JN (1982) Cholecystokinin appears to have antipsychotic properties. Prog Neuropsychopharmacol Biol Psychiatry 6:509–512Google Scholar
  39. Nair NPV, Bloom DM, Nestoros JN, Schwartz G (1983) Therapeutic efficacy of cholecystokinin in neuroleptic-resistant schizophrenic subjects. Psychopharmacol Bull 19:134–136Google Scholar
  40. Nair NPV, Lal S, Bloom DM (1986) Cholecystokinin and schizophrenia. Prog Brain Res 65:237–258Google Scholar
  41. Nakanishi S (1985) Structure and regulation of the preprotochykinin gene. Trends Neurosci 41–44Google Scholar
  42. Nawa H, Kotanie H, Nakanishi S (1984) Tissue-specific generation of two proprotachykinin mRNAs from one gene by alternative RNA splicing. Nature 312:729–734Google Scholar
  43. Nebes RD, Reynolds CF III, Horn LC (1984) The effect of vasopressin on memory in the healthy elderly. Psychiatry Res 11:49–59Google Scholar
  44. Nemeroff CB, Kalivas PW, Golden RN, Prange AJ Jr (1984) Behavioral effects of hypothalamic hypophysiotropic hormones, neurotensin, substance P and other neuropeptides. Pharmacol Ther 24:1–56Google Scholar
  45. Niesink RJM, Van Ree JM (1983) Normalizing effect of an adrenocorticotropic hormone (4–9) analog ORG 2766 on disturbed social behavior in rats. Science 221:960–962Google Scholar
  46. Nyakas C, Veldhuis HD, De Wied D (1985) Beneficial effect of chronic treatment with Org 2766 and a-MSH on impaired reversal learning of rats with bilateral lesions of the parafascicular area. Brain Res Bull 15:257–265Google Scholar
  47. Pedersen RC, Ling N, Brownie AC (1982) Immunoreactive-γ-melanotropin in rat pituitary and plasma: a partial characterization. Endocrinology 110:825–834Google Scholar
  48. Pigache RM, Rigter H (1981) Effects of peptides related to ACTH on mood and vigilance in man. In: Van Wimersma Greidanus TjB, Rees JH (eds) Frontiers of hormone research, vol 8. Karger, Basel, pp 193–207Google Scholar
  49. Prange AJ Jr, Garbutt JC, Loosen PT, Bissette G, Nemeroff ChB (1987) The role of peptides in affective disorders: a review. Prog Brain Res 72:235–247Google Scholar
  50. Reichlin S (1986) Neural functions of TRH. Acta Endocrinol 112[Suppl 276]:21–33Google Scholar
  51. Rosenfeld MG, Mermod JJ, Amara SG, Swanson LW, Sawchenko PE, Rivier J, Vale WW, Evans RM (1983) Production of a novel neuropeptides encoded by the calcitoningene via tissue-specific RNA processing. Nature 304:129–135Google Scholar
  52. Schoemaker H, Davis TP (1984) Differential in vitro metabolism of β-endorphin in schizophrenia. Peptides 5:1049–1054Google Scholar
  53. Tamminga CA, Tighe PJ, Chase TN, DeFraites EG, Schaffer MH (1981) Des-tyrosine-γ-endorphin administration in chronic schizophrenics. Arch Gen Psychiatry 38:167–168Google Scholar
  54. Van Nispen JW, Greven HM (1986) Structure-activity relationships of peptides derived from ACTH, β-LPH and MSH with regard to avoidance behavior. In: De Wied D, Gispen WH, Van Wimersma Greidanus TjB (eds) Neuropeptides and behavior, vol 1. Pergamon, Oxford, pp 349–383Google Scholar
  55. Van Ree JM (1987) Reward and abuse: Opiates and neuropeptides. In: Engel J, Oreland L (eds) Brain reward systems and abuse. Raven, New York, pp 75–88Google Scholar
  56. Van Ree JM, De Wied D (1982) Neuroleptic-like profile of γ-type endorphins as related to schizophrenia. TIPS 3:358–361Google Scholar
  57. Van Ree JM, De Wied D (1983) Behavioral effects of endorphins — modulation of opiate reward by neuropeptides related to pro-opiocortin and neurohypophyseal hormones. In: Smith JE, Lane JD (eds) The neurobiology of opiate reward processes. Elsevier Biomedical Press, Amsterdam, pp 109–145Google Scholar
  58. Van Ree JM, Wolterink G (1987) The ACTH-(4–9) analog Org 2766 accelerates functional recovery following brain lesions. Abstracts Xth Int Congress Pharmacology Sydney, Australia August 23–28, 1987, O 405Google Scholar
  59. Van Ree JM, Bohus B, De Wied D (1980) Similarity between behavioral effects of Des-tyrosine-γ-endorphin and haloperidol and of α-endorphin and amphetamine. In: Leong Way E (ed) Endogenous and exogenous opiate agonists and antatonists. Pergamon, New York, pp 459–462Google Scholar
  60. Van Ree JM, Verhoeven WMA, De Wied D, Van Praag HM (1982) The use of the synthetic peptides y-type endorphins in mentally ill patients. Ann NY Acad Sci 398:478–495Google Scholar
  61. Van Ree JM, Verhoeven WMA, Brouwer GJ, De Wied D (1984) Ceruletide resembles antipsychotics in rats and schizophrenic patients. Neuropsychobiology 12:4–8Google Scholar
  62. Van Ree JM, Hijman R, Jolles J, De Wied D (1985a) Vasopressin and related peptides: animal and human studies. Prog Neuropsychopharmacol Biol Psychiatry 9:551–559Google Scholar
  63. Van Ree JM, Verhoeven WMA, De Wied D (1985b) γ-Type endorphins: neurolepticum-like and antipsychotic action. Prog Neuropsychopharmacol Biol Psychiatry 9:561–567Google Scholar
  64. Van Ree JM, Verhoeven WMA, Claas FHJ, De Wied D (1986) Antipsychotic action of γ-type endorphins: animal and human studies. Prog Brain Res 65:221–235Google Scholar
  65. Veldhuis HD, De Wied D (1984) Differential behavioral actions of corticotropin-releasing factor (CRF). Pharmacol Biochem Behav 21:707–713Google Scholar
  66. Verhoeven WMA, Westenberg HGM, Van Ree JM (1986) A comparative study on the antipsychotic properties of desenkephalin-γ-endorphin and ceruletide in schizophrenic patients. Acta Psychiatr Scand 73:373–382Google Scholar
  67. Volavka J, Hui KS, Anderson B, Nemer Z, O'Donnell J, Lajtha A (1983) Short-lived effect of (des-tyr)-gammaendorphin in schizophrenia. Psychiatry Res 10:243–252Google Scholar
  68. Walter R, Hoffmann PL, Flexner JB, Flexner LB (1975) Neurohypophyseal hormones, analogs, and fragments: their effect on puromycin-induced amnesia. Proc Natl Acad Sci USA 72:4180–4184Google Scholar
  69. Wiegant VM, Burbach JPH, Gaffori O, Verhoef J, Kovács GL, Verhoeven WMA, Van Ree JM, De Wied D (1989)γ-Endorphin with diviant biological activity: a molecular marker for schizophrenia? In: Den Boer NC, Van der Heiden C, Leynse B, Souveryn JHM (eds) Clinical chemistry — an overview. Plenum Press, New York, pp 707–713Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • David de Wied
    • 1
  • Jan M. van Ree
    • 1
  1. 1.Rudolf Magnus Institute for Pharmacology, Medical Faculty University of UtrechtUtrechtThe Netherlands

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