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Serotonin pp 681-705 | Cite as

Studies on the Role of Central 5-HT Neurons in Avoidance Learning: A Behavioral and Biochemical Analysis

  • S. O. Ögren
  • K. Fuxe
  • T. Archer
  • H. Hall
  • A.-C. Holm
  • C. Köhler
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 133)

Abstract

The ascending 5-hydroxytryptamine (5-HT, serotonin) containing neurons first described by Fuxe et al.1, which originate in the midbrain raphe nuclei and have a widespread distribution in the forebrain2,3 have been implicated in avoidance learning and memory processes 4,5,6,7,8,9. Treatments known to modulate 5-HT neurotransmission have been found to alter the acquisition and performance of a wide range of aversively motivated behaviors10,11. Despite intensive research, however, the specific role of serotonin in aversive learning and memory processes is little understood. In recent years it has become increasingly clear that different methods used to manipulate 5-HT neurotransmission can produce highly variable effects on avoidance behavior in the rat even when the animals are tested in similar behavioral situations11,12,13. The available data suggest that the variations in avoidance behavior following 5-HT manipulation depend on both the tools employed to alter 5-HT neurotransmission and the behavioral situation used for testing the animals11. The same manipulation of central 5-HT has been shown to cause different effects on avoidance learning when the testing situation is varied. For example, systemic injection of pchlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, has been reported to facilitate one-way avoidance acquisition6,7, but was recently shown not to significantly affect two-way active avoidance acquisition 12. On the other hand, electrolytic lesions of the midbrain raphe nuclei, which produce a marked reduction in forebrain 5-HT concentrations, but in contrast to PCPA do not affect peripheral 5-HT stores, have consistently been shown to facilitate two-way and to impair one-way avoidance acquisition 11,14. Thus, reduction of brain 5-HT concentrations can produce highly variable effects on avoidance learning.

Keywords

Avoidance Learning Median Raphe Nucleus Avoidance Acquisition Midbrain Raphe Midbrain Raphe Nucleus 
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. 1.
    K. Fuxe, Evidence for the existence of monoamine neurons in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system, Acta Physiol. Scand. 64 (Suppl. 247): 37 (1965).Google Scholar
  2. 2.
    C. C. Azmitia and M. Segal, An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat, J. Comp. Neurol. 179: 641 (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    S. A. Lorens and H. C. Guldberg, Regional 5-hydroxy- tryptamine following selective midbrain raphe lesions in the rat, Brain Res. 78: 45 (1974).PubMedCrossRefGoogle Scholar
  4. 4.
    W. B. Essman, Some neurochemical correlates of altered memory consolidation, Trans. N.Y. Acad. Sci. 32: 948 (1970).PubMedCrossRefGoogle Scholar
  5. 5.
    S. A. Lorens and L. M. Yunger, Morphine analgesia, two-way avoidance, and consummatory behaviour following lesions in the midbrain raphe of the rat, Pharmacol. Biochem. Behay. 2: 215 (1974).CrossRefGoogle Scholar
  6. 6.
    S. S. Tenen, The effects of p-chlorophenylalanine, a serotonin depletor, on avoidance acquisition, pain sensitivity and related behaviour in the rat, Psychopharmacologia 10: 204 (1967).PubMedCrossRefGoogle Scholar
  7. 7.
    J. F. Brody, Jr., Behavioural effects of serotonin depletion and of p-chlorophenylalanine (a serotonin depletor) in rats, Psychopharmacologia 17: 14 (1970).PubMedCrossRefGoogle Scholar
  8. 8.
    S. O. Ogren, Ch. Köhler, S. B. Ross, and B. Srebro, 5-hydroxytryptamine depletion and avoidance acquisition in the rat. Antagonism of the long-term effects of p-chloroamphetamine with a selective inhibitor of 5-hydroxytryptamine uptake, Neuroscience Letters 3: 341 (1976).PubMedCrossRefGoogle Scholar
  9. 9.
    A. V. Rake, Involvement of biogenic amines in memory formation: The central nervous system indole amine involvement, Psychopharmacologia 29: 91 (1973).PubMedCrossRefGoogle Scholar
  10. 10.
    R. B. Messing, D. J. Pettibone, N. Kaufman, and L.D. Lytle, Behavioural effects of serotonin neuro-toxins: An overview, in: “Serotonin neurotoxins,” J. H. Jacoby and L. 67-Lytle, The New York Academy of Sciences, New York (1978).Google Scholar
  11. 11.
    S. A. Lorens, Some behavioural effects of serotonin depletion depend on method: A comparison of 5,7dihydroxytryptamine, p-chlorophenylalanine, pchloroamphetamine, and electrolytic raphe lesions, in: “Serotonin neurotoxins,” J. H. Jacoby and L. D. Lytle, The New York Academy of Sciences, New York (1978).Google Scholar
  12. 12.
    Ch. Köhler and S. A. Lorens, Open field activity and avoidance behaviour following serotonin depletion: a comparison of the effects of parachlorophenylalanine and electrolytic midbrain raphe lesions, Pharmacol. Biochem. Behay. 8: 223 (1978).CrossRefGoogle Scholar
  13. 13.
    S. 0. Ogren and S. B. Ross, Effects of reduced cerebral serotonin on learning, Brain Res. 127: 379 (1977).CrossRefGoogle Scholar
  14. 14.
    B. Srebro and S. A. Lorens, Behavioural effects of selective midbrain raphe lesions in the rat, Brain Res. 89: 303 (1975).PubMedCrossRefGoogle Scholar
  15. 15.
    H. G. Baumgarten and L. Lachenmayer, 5,7-Dihydroxytryptamine: improvement in chemical lesioning of indoleamine neurons in the mammalian brain, Z. Zellforsch. 135: 399 (1972).CrossRefGoogle Scholar
  16. 16.
    E. Sanders-Bush, J. A. Bushing, and F. Sulser, Longterm effects of p-chloroamphetamine on tryptophanhydroxylase activity and on the levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid in brain. Europ. J. Pharmacol. 20: 385 (1972).CrossRefGoogle Scholar
  17. 17.
    R. W. Fuller and B. B. Molloy, Recent studies with 4-chloroamphetamine and some analogues, in: “Advanc. Biochem. and Psychopharmacol., E. Costa, G. L. Gessa, and M. Sandler, Raven Press, New York (1974).Google Scholar
  18. 18.
    G. R. Breese and B. R. Cooper, Behavioural and biochemical interactions of 5,7-dihydroxytryptamine with various drugs when administered intracisternally to adult and developing rats, Brain Res. 98: 517 (1975).PubMedCrossRefGoogle Scholar
  19. 19.
    K. Hole, K. Fuxe, and G. Jonsson, Behavioural effects of 5,7-dihydroxytryptamine lesions of ascending 5-hydroxytryptamine pathways, Brain Res. 107: 385 (1976).PubMedCrossRefGoogle Scholar
  20. 20.
    K. Fuxe, S. O. Ogren, L. F. Agnati, G. Jonsson, and J. A. Gustafsson, 5,7-Dihydroxytryptamine as a tool to study the functional role of central 5hydroxytryptamine neurons, in: “Serotonin neuro-toxins,” J. H. Jacoby and L7-D. Lytle, , The New York Academy of Sciences, New York (1978).Google Scholar
  21. 21.
    S. A. Lorens, H. C. Guldberg, K. Hole, Ch. Köhler, and B. Srebro, Activity, avoidance learning and regional 5-hydroxytryptamine following intrabrainstem 5,7-dihydroxytryptamine and electrolytic midbrain raphe lesions in the rat, Brain Res. 108: 97 (1976).PubMedCrossRefGoogle Scholar
  22. 22.
    A. Björklund, H. G. Baumgarten, and H. G. Rensch, 5,7-Dihydroxytryptamine: improvement of its selectivity for serotonin neurons in the CNS by pretreatment with desipramine, J. Neurochem. 24: 833 (1975).PubMedGoogle Scholar
  23. 23.
    S. O. Ogren, S. B. Ross, and L. Baumann, 5-Hydroxytryptamine and learning: long-term effects of p-chloroamphetamine on acquisition, Med. Biol. 53: 165 (1975).Google Scholar
  24. 24.
    S. O. Ogren, S. B. Ross, A. C. Holm, and L. Baumann, 5-Hydroxytryptamine and avoidance performance in the rat. Antagonism of the acute effect of pchloroamphetamine by zimelidine, an inhibitor of 5-hydroxytryptamine uptake. Neuroscience Letters 3: 331 (1977).Google Scholar
  25. 25.
    J. A. Harvey, S. E. McMaster, and L. M. Yunger, p-Chloroamphetamine: selective neurotoxic action in brain, Science 187: 841 (1975).PubMedCrossRefGoogle Scholar
  26. 26.
    Ch. Köhler, S. B. Ross, B. Srebro, and S. O. Ogren, Long-term biochemical and behavioural effects of p-chloroamphetamine in the rat, in: “Serotonin neurotoxins,” J. H. Jacoby and L. D. Lytle, , The New York Academy of Sciences, New York (1978).Google Scholar
  27. 27.
    S. B. Ross, Antagonism of the acute and long-term biochemical effects of 4-chloroamphetamine on the 5-HT neurons in the rat brain by inhibitors of the 5-hydroxytryptamine uptake, Acta Pharmacol. Toxicol. 39: 456 (1976).Google Scholar
  28. 28.
    S. 0. Ogren and S. B. Ross, Substituted amphetamine derivatives. II. Behavioural effects in mice related to monoaminergic neurons, Acta Pharmacol. Toxicol. 41: 353 (1977)CrossRefGoogle Scholar
  29. 29.
    M. E. Trulson and B. L. Jacobs, Behavioural evidence for the rapid release of CNS serotonin by PCA and fenfluramine, Eur. J. Pharmacol. 36: 149 (1976).PubMedCrossRefGoogle Scholar
  30. 30.
    C. A. Marsden, J. Conti, E. Strope, G. Curzon, and R. N. Adams, Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanaesthetized rat using in vivo voltammetry, Brain Res. 171: 85 (1979).PubMedCrossRefGoogle Scholar
  31. 31.
    E. Sanders-Bush and L. R. Steranka, Immediate and long-term effects of p-chloroamphetamine on brain amines in: “Serotonin neurotoxins,” J. H. Jacoby and L. D. Lytle, , The New York Academy of Sciences (1978).Google Scholar
  32. 32.
    S. B. Ross, S. 0. Ogren, and A. L. Renyi, (Z)-Dimethylamino- 1-(4-bromophenyl)-1-(3-pyridyl)propene (H 102/091, a new selective inhibitor of the neuronal 5-hydroxytryptamine uptake, Acta Pharmacol. Toxicol. 39: 152 (1976).Google Scholar
  33. 33.
    C. Atack and T. Magnusson, A procedure for the isolation of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from the same tissue sample using a single column of strongly acidic cation exchange resin, Acta Pharmacol. Toxicol. 42: 35 (1978).Google Scholar
  34. 34.
    O. H. Lowry, N. J. Rosebrough, A. Farr, and R. J. Randall, Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193: 265 (1951).PubMedGoogle Scholar
  35. 35.
    J. P. Bennett and S. H. Snyder, Serotonin and lysergic acid diethylamide binding in rat brain membranes: relationship to postsynaptic serotonin receptors, Mol. Pharmacol. 12: 373 (1976).Google Scholar
  36. 36.
    H. Hall, and L. Thor, Evaluation of a semiautomatic filtration technique for receptor binding studies, Life Sci. 24: 2293 (1979).PubMedCrossRefGoogle Scholar
  37. 37.
    R. M. Stewart, J. H. Growdon, D. Cancian, and R. J. Baldessarini, 5-Hydroxytryptophan induced myoclonus: increased sensitivity to serotonin after intracranial 5,7-dihydroxytryptamine in the adult rat, Neuropharmacol. 15: 449 (1976).CrossRefGoogle Scholar
  38. 38.
    D. L. Nelson, A. Herbet, S. Bourgoin, J. Glowinski, and M. Hamon, Characteristics of central 5-HT receptors and their adaptive changes following intracerebral 5,7-dihydroxytryptamine administra- tion in the rat, Mol. Pharmacol. 14: 983 (1978).Google Scholar
  39. 39.
    S., O. ögren, and K. Fuxe, On the role of brain nor-adrenaline and the pituitary adrenal axis in learning. I. Studies with corticosterone, Neuroscience Letters 5: 291 (1977).PubMedCrossRefGoogle Scholar
  40. 40.
    S., T. Mason, and H. C. Fibiger, Noradrenaline and avoidance learning in the rat, Brain Res. 161: 321 (1979).PubMedCrossRefGoogle Scholar
  41. 41.
    H., C. Fibiger, and B. A. Campbell, The effect of para-chlorophenylalanine on spontaneous locomotor activity in the rat, Neuropharmacol. 10: 25 (1971).CrossRefGoogle Scholar
  42. 42.
    A., H. Black, L. Nadel, and J. O’Keefe, Hippocampal function in avoidance learning and punishment, Psychological Bulletin 84: 1107 (1977).PubMedCrossRefGoogle Scholar
  43. 43.
    D., A. V. Peters, H. Anisman, and B. A. Pappas, Monoamines and aversively motivated behaviours, in: “Psychopharmacology of aversively motivated behaviour,” H. Anisman and G. Bignami, , Springer Science+Business Media New York (1978).Google Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • S. O. Ögren
    • 1
  • K. Fuxe
    • 2
  • T. Archer
    • 1
  • H. Hall
    • 1
  • A.-C. Holm
    • 1
  • C. Köhler
    • 1
  1. 1.Research and Development LaboratoriesAstra Läkemedel ABSödertäljeSweden
  2. 2.Department of HistologyKarolinska InstituteStockholmSweden

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