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Serotonin pp 125-151 | Cite as

The Role of Serotonin in Modulation of Nociceptive Reflexes

  • John A. Harvey
  • Kenny J. Simansky
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 133)

Abstract

During the past fifteen years, a variety of evidence has accumulated which is consistent with the Brodie and Shore (1957) hypothesis that serotonergic neurons in the central nervous system serve a tropotrophic role (Hess, 1954) in inhibiting an animal’s response to diverse arousing stimuli (Harvey et al., 1975). This role for serotonin is, perhaps, most thoroughly documented in studies dealing with an animal’s responsé to painful stimuli. The results of numerous studies suggest that decreases in serotonergic activity result in hyperalgesia while increases produce analgesia (Harvey et al., 1975; Mayer and Price, 1976; Messing and Lytle, 1977). Thus one can assume that painful stimuli normally lead to increased activity within the serotonergic system which partially inhibits or diminishes the intensity of the nociceptive reflex. This view of the role of serotonin in determining an animal’s response to painful stimuli has resulted from the application of a wide variety of techniques for altering serotonergic function in the central nervous system and for assessing pain sensitivity. Such a convergent approach is important, since no single technique can be relied on to produce an alteration in serotonergic function without also having additional effects, some of which are known and others yet to be discovered. Similarly, since pain is not a unitary phenomenon, there is no a priori reason for assuming that serotonin should have an equivalent inhibitory effect on all nociceptive reflexes. In fact, since different nociceptive reflexes involve different portions of the central nervous system, it would be more surprising if some form of selectivity did not exist. Most investigators, including ourselves, have sometimes ignored these caveats by placing too great a reliance on a single procedure for altering serotonergic function or for assessing pain sensitivity. As a result the precise role of serotonin in determining an animal’s response to painful stimuli has recently been obscured by conflicting conclusions and apparently contradictory data. Accordingly, this paper will review the evidence concerning the role of serotonin in nociception, with special attention given to the means employed for altering serotonergic function and assessing pain sensitivity.

Keywords

Pain Sensitivity Septal Lesion Medial Forebrain Bundle Brain Serotonin Electrolytic Lesion 
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. Agid, Y., Javoy, F., Glowinski, J., Bouvet, D., and Sotelo, C., 1973, Injection of 6-hydroxydopamine into the substantia nigra of the rat. II. Diffusion and specificity, Brain Research, 58: 291–301.PubMedCrossRefGoogle Scholar
  2. Björklund, A., Baumgarten, H. G., and Rensch, A., 1975, 5,7dihydroxytryptamine: improvement of its selectivity for serotonin neurons in the CNS by treatment with desipramine, Journal of Neurochemistry, 24:833–835.Google Scholar
  3. Bläsig, J., Reinhold, K., and Herz, A., 1973, Effect of 6-hydroxydopamine, 5,6-dihydroxytryptamine and raphe lesions on the entinoceceptive actions of morphine in rats, Psychopharmacologia, 31: 111–119.PubMedCrossRefGoogle Scholar
  4. Breese, G. R., and Mueller, R. A., 1978, Alterations in the neurocytoxicity of 5,7-dihydroxytryptamine by pharmacologic agents in adult and developing rats, Annals of the New York Academy of Sciences, 305: 160–174.PubMedCrossRefGoogle Scholar
  5. Brodie, B. B., and Shore, P. A., 1957, A concept for the role of serotonin and norepinephrine as chemical mediators in the brain, Annals of the New York Academy of Sciences, 66: 631–642.PubMedCrossRefGoogle Scholar
  6. Buxbaum, D. M., Yarbrough, G. G., and Carter, M. E., 1973, Biogenic amines narcotic effects. I. Modification of morphine-induced analgesia and motor activity after alteration of cerebral amine levels, Journal of Pharmacology and Experimental Therapeutics, 185: 317–327.PubMedGoogle Scholar
  7. Carnegie, P. R., 1971, Properties, structure and possible neuro-receptor role of the encephalitogenic protein of human brain, Nature (London), 229: 25–28.CrossRefGoogle Scholar
  8. Cheney, D. L., and Goldstein, A., 1971, The effect of -chlorophenylalanine on opiate-induced running, analgesia, tolerance, and physical dependence in mice, Journal of Pharmacology and Experimental Therapeutics, 177: 309–315.PubMedGoogle Scholar
  9. Christenson, J. G., Dairman, W., and Udenfriend, S., 1972, On the identity of DOPA decarboxylase and 5-hydroxytryptophan de-carboxylase, Proceedings of the National Academy of Science (USA), 69: 343–347.CrossRefGoogle Scholar
  10. Corrodi, H., Fuxe, K., and Schou, M., 1969, The effect of prolonged lithium administration on cerebral monoamine neurons in the rat, Life Science, (Part I), 8: 643–651.Google Scholar
  11. Coscina, D. V., Warsh, J. J., Godse, D. P., and Stancer, H. S., 1974, Nonspecifícity of 5-hydroxytryptophan in repleting brain serotonin in rats with MFB lesions, Research Communications in Chemistry, Pathology, and Pharmacology, 1: 617–620.Google Scholar
  12. Dennis, M., 1972, Sex-dependent and sex-independent neural control of reactivity to electric foot shock in the rat. Experimental Neurology, 37: 256–268.PubMedCrossRefGoogle Scholar
  13. Evans, W. O., 1961, A new technique for the investigation of some analgesic drugs on a reflexive behavior in the rat. Psychopharmacologia, 2: 318–325.CrossRefGoogle Scholar
  14. Fíbiger, H. C., Mertz, P. H., and Campbell, B. A., 1972, The effect of para-chlorophenylalanine on aversive thresholds and reactivity to foot shock, Physiology and Behavior, 8: 259–263.PubMedCrossRefGoogle Scholar
  15. Fuller, R. W., Perry, K. W., Snoddy, H. D., and Molloy, B. B., 1974, Comparison of the specificity of 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine and chlorimipramine as amine uptake inhibitors in mice, European Journal of Pharmacology, 28: 233–236.PubMedCrossRefGoogle Scholar
  16. Fuller, R. W., Snoddy, H. D., and Molloy, B. B., 1975, Blockade of amine depletion by nísoxetine in comparison to other uptake inhibitors, Psychopharmacology Communications, 1: 455–464.PubMedGoogle Scholar
  17. Fuller, R. W., and Wong, D. T., 1977, Inhibition of serotonin reuptake, Federation Proceedings, 36: 2154–2158.PubMedGoogle Scholar
  18. Fuxe, K., 1965, Evidence for the existence of monoamine neurons in the central nervous systems. IV. Distribution of monoamine nerve terminals in the central nervous system. Acta Physiologica Scandinavica, Supplementum 247: 39–85.Google Scholar
  19. Fuxe, K., Butcher, L. L., and Engel, J., 1971, DL-5-hydroxytryptophan-induced changes in central monoamine/neurons after peripheral decarboxylase inhibition, Journal of Pharmacy and Pharmacology, 23: 420–424.PubMedCrossRefGoogle Scholar
  20. Fuxe, K., and Jonsson, G., 1974, Further mapping of central 5-hydroxytryptamine neurons: studies with the neurotoxic dihydroxytryptamines, Advances in Biochemical Psychopharmacology, 10: 1–12.PubMedGoogle Scholar
  21. Fuxe, K.A Ogren, S.-E., Agnati, L. F., Jonsson, G., and Gustafsson, J.-X., 1978, I5,7-dihydroxytryptamine as a tool to study the functional role of central 5-hydroxytryptamine neurons, Annals of the New York Academy of Sciences, 305: 346–369.Google Scholar
  22. Gallager, D. W., and Aghajanian, G. K., 1976, Inhibition of firing of raphe neurones by tryptophan and 5–hydroxytryptophan: blockade by inhibiting serotonin synthesis with R0–4–4602, Neuropharmacology, 15: 149 – 156.PubMedCrossRefGoogle Scholar
  23. Garau, L., Mulas, M. L., and Pepeu, G., 1975, The influence of raphe lesions on the effect of morphine on nociception and cortical Ach output, Neuropharmacology, 14: 259–263.PubMedCrossRefGoogle Scholar
  24. Gerson, S., and Baldessarini, R. J., 1975, Selective destruction of serotonin terminals in rat forebrain by high doses of 5,7dihydroxytryptamine, Brain Research, 85: 140–145.CrossRefGoogle Scholar
  25. Gerson, S., Baldessarini, R. J., and Wheeler, S. C., 1974, Biochemical effects of dihydroxylated tryptamines on central indoleamine neurones, Neuropharmacology, 13: 987–1004.PubMedCrossRefGoogle Scholar
  26. Geyer, M. A., Puerto, A., Dansey, W. J., Knapp, S., Bullard, W. P., and Mandell, A. J., 1976, Histologic and enzymatic studies of the mesolimbic and mesostriatal serotonergic pathways, Brain Research, 106: 241–256.PubMedCrossRefGoogle Scholar
  27. Grahame-Smith, D. G., 1973, Does the total turnover of brain 5-HT reflect the functional activity of 5-HT in brain?, in: “Serotonin and Behavior,” J. Barchas and E. Usdin, eds., Academic Press, New York.Google Scholar
  28. Haigler, H. J., and Aghajanian, G. K., 1974, Peripheral serotonin antagonists: failure to antagonize serotonin in brain areas receiving a prominent serotonergic input, Journal of Neural Transmission, 35: 257–273.CrossRefGoogle Scholar
  29. Haigler, H. J., and Aghajanian, G. K., 1977, Serotonin receptors in the brain, Federation Proceedings, 36: 2159–2164.PubMedGoogle Scholar
  30. Halaris, A. E., Jones, G. G., and Moore, R. Y., 1976, Axonal transport in serotonin neurons of the midbrain raphe, Brain Research, 107, 555–574.PubMedCrossRefGoogle Scholar
  31. Harrison-Read, P. E., and Steinberg, H., 1971, Lithium-induced hypersensitivity to foot shock in rats and the role of 5hydroxytryptophan, Nature (New Biology), 232: 120–121.CrossRefGoogle Scholar
  32. Harvey, J. A., and Gal, E. M., 1974, Septal tryptophan-5-hydroxylase: divergent response to raphe lesions and para-chlorophenylalanine, Science (Washington), 183: 869–871.CrossRefGoogle Scholar
  33. Harvey, J. A., Heller, A., and Moore, R. Y., 1963, The effect of unilateral and bilateral medial forebrain bundle lesions on brain serotonin, Journal of Pharmacology and Experimental Therapeutics, 140: 103–110.PubMedGoogle Scholar
  34. Harvey, J. A., and Lints, C. E., 1965, Lesions in the medial forebrain bundle: delayed effects on sensitivity to electric shock, Science, 148: 250–252.PubMedCrossRefGoogle Scholar
  35. Harvey, J. A., and Lints, C. E., 1971, Lesions in the medial fore- brain bundle: relationship between pain sensitivity and telencephalic content of serotonin, Journal of Comparative and Physiological Psychology, 74: 28–36.PubMedCrossRefGoogle Scholar
  36. Harvey, J. A., Schlosberg, A. J., and Yunger, L. M., 1974, Effect of p-chlorophenylalanine and brain lesions on pain sensitivity and morphine analgesia in the rat, Advances in Biochemical Psychopharmacology, 10: 233–245.PubMedGoogle Scholar
  37. Harvey, J. A., Schlosberg, A. J., and Yunger, L. M., 1975, Behavioral correlates of serotonin depletion, Federation Proceedings, 34: 1796–1801.PubMedGoogle Scholar
  38. Harvey, J. A., and Yunger, L. M., 1973, Relationship between terencephalic content of serotonin and pain sensitivity, in: “Serotonin and Behavior,” J. Barchas and E. Usdin, eds., Academic Press, New York.Google Scholar
  39. Headley, P. M., Duggan, A. W., and Griersmith, B. T., 1978, Selective reduction by noradrenaline and 5-hydroxytryptamine of nociceptive responses of cat dorsal horn neurons, Brain Research, 145: 185–189.PubMedCrossRefGoogle Scholar
  40. Heller, A., and Harvey, J. A., 1963, Effect of CNS lesions on brain norepinephrine, Pharmacologist, 5: 264.Google Scholar
  41. Heller, A., and Moore, R. Y., 1968, Control of brain serotonin and norepinephrine by specific neural systems, Advances in Pharmacology, 6A: 191–206.PubMedCrossRefGoogle Scholar
  42. Hess, W. R., 1954, “Diencephalon, Autonomic and Extraphyramidal Functions,” Grune and Stratton, New York.Google Scholar
  43. Ho, A. K. S., Loh, H. H., Craves, F., Hitzemann, R. J., and Gershon, S., 1970, The effect of prolonged lithium treatment on the synthesis rate and turnover of monoamines in brain regions of rats, European Journal of Pharmacology, 10: 72–78.CrossRefGoogle Scholar
  44. Hókfelt, T., Fuxe, K., and Goldstein, M., 1973, Immunohistochemical localization of aromatic L-amino acid decarboxylase (DOPA de-carboxylase) in central dopamine and 5-hydroxytryptamine nerve cell bodies of the rat, Brain Research, 53: 175–180.PubMedCrossRefGoogle Scholar
  45. Hole, K., Fuxe, K., and Jonsson, G., 1976, Behavioral effects of 5,7-dihycroxytryptamine lesions of ascending 5-hydroxytryptamine pathways, Brain Research, 107: 385–399.PubMedCrossRefGoogle Scholar
  46. Hole, K., and Lorens, S. A., 1975, Response to electric shock in rats: effects of selective midbrain raphe lesions, Pharmacology, Biochemistry, and Behavior, 3: 95–102.PubMedCrossRefGoogle Scholar
  47. Hole, K., and Marsden, C. A., 1975, Unchanged sensitivity to electric shock in L-tryptophan treated rats, Pharmacology, Biochemistry, and Behavior, 3: 307–309.PubMedCrossRefGoogle Scholar
  48. Jonsson, G., Einarsson, P., Fuxe, K., and Hallman, H., 1975, Micro- spectrofluorimetric analysis of the formaldehyde induced fluorescence in midbrain raphe neurons, Medical Biology, 53: 25–39.PubMedGoogle Scholar
  49. Koe, K., 1976, Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain, Journal of Pharmacology and Experimental Therapeutics, 199: 649–661.PubMedGoogle Scholar
  50. Koe, B. K., and Weissman, A., 1966, p-Chlorophenylalanine: a specific depletor of brain serotonin, Journal of Pharmacology and Experimental Therapeutics, 154:499-516.Google Scholar
  51. Kuhar, M. J., Aghajanian, G. K., and Roth, R. H., 1972, Tryptophan hydroxylase activity and synaptosomal uptake of serotonin in discrete brain regions after midbrain raphe lesions: correlations with serotonin levels and histochemical fluorescence, Brain Research, 44: 165–176.PubMedCrossRefGoogle Scholar
  52. Kuraishi, Y., Harada, Y., and Takagi, H., 1979, Noradrenaline regulation of pain-transmission in the spinal cord mediated by alpha-adrenoleptors, Brain Research, 174: 333–336.PubMedCrossRefGoogle Scholar
  53. Lints, C. E., and Harvey, J. A., 1969, Altered sensitivity to foot shock and decreased brain content of serotonin following brain lesions in the rat, Journal of Comparative and Physiological Psychology, 67: 23–31.PubMedCrossRefGoogle Scholar
  54. Lints, C. E., and Harvey, J. A., 1969, Drug induced reversal of brain damage in the rat, Physiology and Behavior, 4: 29–31.CrossRefGoogle Scholar
  55. Lints, C. E., Nenja, L. H., and Miller, J. F., 1979, Stimulusdependent changes in footshock sensitivity following medial forebrain bundle lesions in the rat, Neuroscience Abstracts, 5: 613.Google Scholar
  56. Lorens, S. A., Köhler, C., and Guldberg, H. C., 1975, Lesions in Gudden’s tegmental nuclei produce behavioral and 5-HT effects similar to those after raphe lesions, Pharmacology, Biochemistry, and Behavior, 3: 653–659.PubMedCrossRefGoogle Scholar
  57. Lorens, S. A., Sorenson, J. P., and Harvey, J. A., 1970, Lesions in the nuclei accumbens septi of the rat: behavioral and neurochemical effects, Journal of Comparative and Physiological Psychology, 73: 284–290.PubMedCrossRefGoogle Scholar
  58. Lorenz, H. P., Pieri, L., and Richards, J. G., 1975, Disappearance of supra-ependymal 5-HT axons in the rat forebrain after electrolytic and 5,6-DHT-induced lesions of the medial forebrain bundle, Brain Research, 100: 1–12.CrossRefGoogle Scholar
  59. Lubar, J. F., Brener, J. M., Deagle, J. H., Numan, R., and Clemens, W. J., 1970, Effect of septal lesions on detection threshold and unconditioned response to shock, Physiology and Behavior, 5: 459–463.PubMedCrossRefGoogle Scholar
  60. Lytle, L. D., Messing, R. B., Fisher, L., and Phebus, L., 1975, Effects of long-term corn consumption on brain serotonin and the response to electric shock, Science, 190: 692–694.PubMedCrossRefGoogle Scholar
  61. Margalit, D., and Segal, M., 1979, A pharmacologic study of analgesia produced by stimulation of the nucleus locus coeruleus, Psychopharmacology, 62: 169–173.PubMedCrossRefGoogle Scholar
  62. Mayer, D. J., and Price, D. D., 1976, Central nervous system mechanisms of analgesia, Pain, 2: 379–404.PubMedCrossRefGoogle Scholar
  63. Melzack, R., Stotler, W. A., and Livingston, W. K., 1958, Effects of discrete brainstem lesions in cats on perception of noxious stimulation, Journal of Neurophysiology, 21: 353–367.PubMedGoogle Scholar
  64. Messing, R. B., Fisher, L. A., Phebus, L., and Lytle, L. D., 1976, Interaction of diet and drugs in the regulation of brain 5hydroxyindoles and the response to painful electric shock, Life Sciences, 18: 707–714.PubMedCrossRefGoogle Scholar
  65. Messing, R. B., and Lytle, L. A., 1977, Serotonin-containing neurons: their possible role in pain and analgesia, Pain, 4: 1–21.PubMedCrossRefGoogle Scholar
  66. Messing, R. B., Phebus, L., Fisher, L. A., and Lytle, L. D., 1975, Analgesic effect of fluoxetine hydrochloride (Lilly 110140), a specific inhibitor of serotonin uptake, Psychopharmacplogy Communications, 1: 511–521.Google Scholar
  67. Miczek, K. A., Kelsey, J. E., and Grossman, S. P., 1972, Time course of effects of septal lesions on avoidance, response suppression and reactivity to shock, Journal of Comparative and Physiological Psychology, 79: 318–327.PubMedCrossRefGoogle Scholar
  68. Misantone, L. J., 1976, Effects of damage to the monoamine axonal constituents of the medial forebrain bundle on reactivity to foot shock and ingestive behavior in the rat, Experimental Neurology, 50: 448–464.PubMedCrossRefGoogle Scholar
  69. Moir, A. T. B., and Eccleston, D., 1968, The effects of precursor loading in the cerebral metabolism of 5-hydroxyindoles, Journal of Neurochemistry, 15: 1093–1108.PubMedCrossRefGoogle Scholar
  70. Nauta, W. J. H., 1958, Hippocampal projections and related neural pathways to the midbrain in the cat, Brain, 81: 319–340.PubMedCrossRefGoogle Scholar
  71. Nobin, A., and Björklund, A., 1978, Degenerative effects of various neurotoxic indoleamines on central monoamine neurons, Annals of the New York Academy of Sciences, 305: 305–327.PubMedCrossRefGoogle Scholar
  72. Owman, C., and Rosengren, E., 1967, Dopamine formation in blood capillariesan enzymatic blood-brain barrier mechanism, Journal of Neurochemistry, 14: 547–550.PubMedCrossRefGoogle Scholar
  73. Palkovits, M., Saavedra, J. M., Jacobowitz, D. M., Kizer, J. S., Zaborszky, L., and Brownstein, M. J., 1977, Serotonergic innervation of the forebrain: effect of lesions on serotonin and tryptophan hydroxylase levels, Brain Research, 130: 121–134.PubMedCrossRefGoogle Scholar
  74. Persip, G. L., and Hamilton, L. W., 1973, Behavioral effects of serotonin or a blocking agent applied to the septum of the rat, Pharmacology, Biochemistry, and Behavior, 1: 139–147.CrossRefGoogle Scholar
  75. Rodgers, R. J., 1977, The medial amygdala: serotonergic inhibition of shock-induced aggression and pain sensitivity in rats, Aggressive Behavior, 3: 277–288.CrossRefGoogle Scholar
  76. Schmitt, H., LeDouarec, J.-C., and Petillot, N., 1974, Antinociceptive effects of some alpha-sympathomimetic agents, Neuro-pharmacology, 13: 289–294.Google Scholar
  77. Segal, D. S., 1976, Differential effects of para-chlorophenylalanine on amphetamine-induced locomotion and stereotypy, Brain Research, 116: 267–276.PubMedCrossRefGoogle Scholar
  78. Segal, M., and Sandberg, D., 1977, Analgesia produced by electrical stimulation of catecholamine nuclei in the rat brain, Brain Research, 123: 369–372.PubMedCrossRefGoogle Scholar
  79. Shaskan, E. G., and Snyder, S. H., 1970, Kinetics of serotonin accumulation into slices from rat brain: relationship to catecholamine uptake, Journal of Pharmacology and Experimental Therapeutics, 175: 404–418.PubMedGoogle Scholar
  80. Simansky, K. J., and Harvey, J. A., 1978, Stimulus-dependent changes in pain-sensitivity after central monoamine depletion: hyperalgesia on the hot-plate associated with norepinephrine depletion and in flinch-jump with serotonin depletion, Neuroscience Abstracts, 4: 283.Google Scholar
  81. Simansky, K. J., and Harvey, J. A., 1979, Stimulus-dependent analgesic action of monoamine uptake inhibitors: relationship to 5-HT and NE function in CNS, Neuroscience Abstracts, 5: 353.Google Scholar
  82. Slater, P., 1974, Effect of 6-hydroxydopamine on some actions of tremoríne and oxotremorine, European Journal of Pharmacology, 25: 130–137.PubMedCrossRefGoogle Scholar
  83. Slater, P., and Blundell, C., 1978, The effect of 6-hydroxydopamine on the antinociceptive action of morphine, European Journal of Pharmacology, 48: 237–247.PubMedCrossRefGoogle Scholar
  84. Smith, R. F., 1979, Mediation of footshock sensitivity by serotonergic projection to hippocampus, Pharmacology, Biochemistry, and Behavior, 10: 381–388.PubMedCrossRefGoogle Scholar
  85. Sugrue, M. F., and Mclndewar, I., 1976, Effect of blockade of 5hydroxytryptamine reuptake on drug-induced antinociception in the rat, Journal of Pharmacy and Pharmacology, 28: 447–448.PubMedCrossRefGoogle Scholar
  86. Tagliamonte, A., Tagliamonte, P., Corsini, G. U., Mereu, G. P., and Gessa, G. L., 1973, Decreased conversion of tyrosine to catecholamines in the brain of rats treated with p-chlorophenylalanine, Journal of Pharmacy and Pharmacology, 25: 101–103.PubMedCrossRefGoogle Scholar
  87. Telner, J., Lepore, F., and Guillemot, J.-P., 1979, Effects of serotonin content on pain sensitivity in the rat, Pharmacology, Biochemistry, and Behavior, 10: 657–661.PubMedCrossRefGoogle Scholar
  88. Tenen, S. S., 1967, The effects of p-chlorophenylalanine, a serotonin depletor, on avoidance acquisition, pain sensitivity and related behavior in the rat, Psychopharmacologia, 10: 204–219.PubMedCrossRefGoogle Scholar
  89. White, S. R., White, F. P., Barnes, C. D., and Albright, J. F., 1973, Increased shock sensitivity in rats with experimental allergic encephalomyelitis and reversal by 5-hydroxytryptophan, Brain Research, 58: 251–254.PubMedCrossRefGoogle Scholar
  90. Wong, D. T., Bymaster, F. P., Horng, J. S., and Molloy, B. B., 1975, A new selective inhibitor for uptake of serotonin into synaptosomes of rat brain: 3-(p-Trifluoromethylphenoxy)-Nmethyl-3-phenylpropylamine, Journal of Pharmacology and Experimental Therapeutics, 193: 804–811.PubMedGoogle Scholar
  91. Wong, D. T., Horng, J. S., Bymaster, F. P., Hauser, K. L., and Molloy, B. B., 1974, A selective inhibitor of serotonin uptake: Lilly 110140, 3-(p trifluoromethylphenoxy)-N-methyl-3phenylpropylamine, Life Sciences, 15: 471–479.PubMedCrossRefGoogle Scholar
  92. Yaksh, T. L., and Wilson, P. R., 1979, Spinal serotonin system mediates antinociception, Journal of Pharmacology and Experimental Therapeutics, 208: 446–453.PubMedGoogle Scholar
  93. Yunger, L. M., and Harvey, J. A., 1973, Effect of lesions in the medial forebrain bundle on three measures of pain sensitivity and noise-elicited startle, Journal of Comparative and Physiological Psychology, 83, 173–183.PubMedCrossRefGoogle Scholar
  94. Yunger, L. M., and Harvey, J. A., 1976, Kinetic analysis of 3Hserotonin accumulation in four regions of rat brain after lesions in the medial forebrain bundle, Life Sciences, 19: 105–116.PubMedCrossRefGoogle Scholar
  95. Yunger, L. M., and Harvey, J. A., 1976, Behavioral effects of L-5hydroxytryptophan after destruction of ascending serotonergic pathways in the rat: the role of catecholaminergic neurons, Journal of Pharmacology and Experimental Therapeutics, 196: 307–315.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • John A. Harvey
    • 1
  • Kenny J. Simansky
    • 2
  1. 1.Department of Psychology and PharmacologyThe University of IowaIowa CityUSA
  2. 2.Department of PsychiatryNew York Hospital Cornell Medical CenterWhite PlainsUSA

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