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Cognitive Therapy and Research

, Volume 22, Issue 6, pp 595–613 | Cite as

Stressor Controllability, Anxiety, and Serotonin

  • Steven F. Maier
  • Linda R. Watkins
Article

Abstract

It is argued that exposure to stressors cansensitize the neural machinery that mediates fear for aperiod of time, and that during this time period fearconditioning is potentiated and responses to ambiguous or mildly fearful stimuli are exaggerated. Thecontrollability of the stressor is a key characteristicof the stressor which determines whether thissensitization occurs. That is, sensitization follows exposure to uncontrollable, but not tocontrollable, stressors. It is argued that thissensitization of the neural structures that mediate fearmay be similar to what is meant by anxiety, and thatbrain serotonin systems are a key component of thissensitization process. The implications of this point ofview for a variety of phenomena including learnedhelplessness and reactivity to drugs of abuse are discussed.

ANXIETY FEAR STRESS LEARNED HELPLESSNESS STRESSOR CONTROLLABILITY SEROTONIN AMYGDALA DORSAL RAPHE NUCLEUS 

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REFERENCES

  1. Anisman, H., Zalcman, S., Shanks, N., & Zacharko, R. M. (1991). Multisystem regulation of performance deficits induced by stressors: An animal model of depression. Clifton, NJ: Humana Press.Google Scholar
  2. Behbehani, M. M. (1995). Functional characteristics of the midbrain periaqueductal gray. Progress in Neurobiology, 46, 575–605.CrossRefPubMedGoogle Scholar
  3. Blanchard, D. C., & Blanchard, R. J. (1972). Innate and conditioned reactions to threat in rats with amygdaloid lesions. Journal of Comparative Physiology and Psychology, 81, 281–290.Google Scholar
  4. Blanchard, D. C., & Blanchard, R. J. (1988). Ethoexperimental approaches to the biology of emotion. Palo Alto, CA: Annual Reviews.Google Scholar
  5. Bolles, R. C., & Fanselow, M. S. (1980). A perceptual-defensive-recuperative model of fear and pain. Behavioral and Brain Sciences, 3, 291–301.Google Scholar
  6. Campeau, S., Hayward, M. D., Hope, B. T., Rosen, J. B., Nestler, E. J., & Davis, M. (1991). Induction of c-fosproto-oncogene in rat amygdala during unconditioned and conditioned fear. Brain Research, 565, 349–352.CrossRefPubMedGoogle Scholar
  7. Costa, E., & Guidotti, A. (1991). Diazepam binding inhibitor (DBI): A peptide with multiple biological actions. Life Science, 49, 325–344.CrossRefGoogle Scholar
  8. Davis, M. (1992). The role of the amygdala in fear and anxiety. Annual Review of Neuroscience, 15, 353–375.CrossRefPubMedGoogle Scholar
  9. Davis, M., Cassella, J. V., & Kehne, J. H. (1988). Serotonin does not mediate anxiolytic effects of buspirone in the fear-potentiated startle paradigm: Comparison with 8-OHDPAT and ipsapirone. Psvchopharmacology, 94, 14–20.Google Scholar
  10. DeVry, J. ( 1995). 5-HT1A receptor agonists: Recent developments and controversial issues. Psychopharmacology, 121, 1–26.PubMedGoogle Scholar
  11. Desiderato, O., & Newman, A. (1971). Conditioned suppression produced in rats by tones paired with escapable or inescapable shock. Journal of Comparative Physiology and Psychology, 77, 427–443.Google Scholar
  12. Dess, N.K., Minor, T. R., & Brewer, J. (1989). Suppression of feeding and body weight by inescapable shock: Modulation by quinine adulteration, stress reinstatement, and stressor controllability. Physiology and Behavior, 45, 975–983.CrossRefPubMedGoogle Scholar
  13. Dorow, R. (1982). b-carboline monomethylamide causes anxiety in man. CINP Congress Jerusalem, 13, 176.Google Scholar
  14. Drugan, R. C., & Holmes, P. V. (1991). Central and peripheral benzodiazepine receptors: Involvement in an organism's response to physical and psychological stress. Neuroscience and Biobehavioral Reviews, 15, 277–298.PubMedGoogle Scholar
  15. Drugan, R. C., Morrow, A. L., Weizman, R., Weizman, A., Deutsch, S. I., Crawley, J. N., & Paul, S. M. (1989). Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy. Brain Research, 487, 45–51.CrossRefPubMedGoogle Scholar
  16. Drugan, R. C., Ryan, S. M., Minor, T. R., & Maier, S. F. (1984). Librium prevents the analgesia and shuttlebox escape deficit typically observed following inescapable shock. Pharmacology Biochemistry and Behavior, 21, 749–754.Google Scholar
  17. Duxon, M. S., Flanigan, T. P., Reavley, A. C., Baxter, G. S., Blackburn, T. P., & Fone, K. C. (1997). Evidence for expression of the 5-hydroxytryptamine-2B receptor protein in the rat central nervous system. Neuroscience, 76, 323–329.CrossRefPubMedGoogle Scholar
  18. Edwards, E., Harkins, K., Wright, G., & Henn, F. (1991). Modulation of [3H]paroxetine binding to the 5-hydroxytryptamine uptake site in an animal model of depression. Journal of Neurochemistry, 56, 1581–1586.PubMedGoogle Scholar
  19. Fanselow, M. S. (1991). The midbrain periaqueductal gray as a coordinator of action in response to fear and anxiety. New York: Plenum Press.Google Scholar
  20. Fanselow, M. S., & Lester, L. S. (1988). A function al behavioristic approach to aversively motivated behavior: Predatory imminence as a determinant of the topography of defensive behavior. Hillsdale, NJ: Erlbaum.Google Scholar
  21. File, S. E. (1980). The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drug. Journal of Neuroscience Methods, 2, 219–238.CrossRefPubMedGoogle Scholar
  22. File, S. F. (1985). Animal models for predicting clinical efficacy of anxiolytic drugs: Social behavior. Neuropsychobiology, 13, 55–62.PubMedGoogle Scholar
  23. Gleitman, H., & Holmes, P. A. (1967). Retention of incompletely learned CER in rats. Psychonomic Science, 7, 19–20.Google Scholar
  24. Gloor, P., Olivier, A., Aiesney, L. F., Andermann, F., & Horowitz, S. (1982). The role of the limbic system in experiential phenomena of temporal lobe epilepsy. Annals of Neurology, 12, 129–144.PubMedGoogle Scholar
  25. Gonzalez, L. E., Andrews, N., & File, S. E. (1996). 5-HT1A and benzodiazepine receptors in the basolateral amygdala modulate anxiety in the social interaction test, but not in the elevated plus-maze. Brain Research, 732, 145–153.CrossRefPubMedGoogle Scholar
  26. Graeff, F. G., Guimaraes, F. S., De Andrade, T. G. C. S., & Deakin, J. F. W. (1996). Role of 5-HT in stress, anxiety, and depression. Pharmacology, Biochemistry and Behavior, 54, 129–141.Google Scholar
  27. Handley, S. L. (1995). 5-Hydroxytryptamine pathways in anxiety and its treatment. Pharmacology and Therapeutics, 66, 103–148.CrossRefPubMedGoogle Scholar
  28. Heidenrich, B. A., Basse-Tomusk, A. E., & Rebec, C. V. (1987). Serotonergic dorsal rapheneurons: Subsensitivity to amphetamine with long-term treatment. Neuropharmacology, 26, 719–724.CrossRefPubMedGoogle Scholar
  29. Higgins, G., Jones, B., Oakley, N., & Tyers, M. (1991). Evidence that the amygdala is involved in the disinhibitory effects of 5-HT3 receptor antagonists. Psychopharmacology, 104, 545–551.PubMedGoogle Scholar
  30. Higgins, G. A., Bradbury, A. J., Jones, B. J., & Oakley, N. R. (1988). Behavioral and biochemical consequences following activation of 5-HT1-like and GABA receptors in the dorsal raphe nucleus of the rat. Neuropharmacology, 27, 993–1001.CrossRefPubMedGoogle Scholar
  31. Hindley, S. W., Hobbs, A., Paterson, I. A., & Roberts, M. H. T. (1985). The effects of methyl b-carboline-3-carboxylate on social interaction and locomotor activity when microinjected into the nucleus raphé dorsalis of the rat. British Journal of Pharmacology, 86, 753–761.PubMedGoogle Scholar
  32. Hitchcock, J. M., & Davis, M. (1986). Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm. Behavioral Neuroscience, 100, 11–22.CrossRefPubMedGoogle Scholar
  33. Hodges, H., Green, S., & Glenn, B. (1987). Evidence that the amygdala is involved in benzodiazepine and serotonergic effects on punished responding but not on discrimination. Psychopharmacology, 92, 491–504.CrossRefPubMedGoogle Scholar
  34. Iversen, S. D. (1984). 5-HT and anxiety. Neuropharmacology, 23, 1553–1560.CrossRefPubMedGoogle Scholar
  35. Jacobs, B. L., & Fornal, C. A. (1993). 5-HT and motor control: A hypothesis. Trends in Neuroscience, 16, 346–352.CrossRefGoogle Scholar
  36. Job, R. F., & Barnes, B. W. (1995). Stress and consumption: Inescapable shock, neophobia, and quinine finickiness in rats. Behavioral Neuroscience, 109, 106–116.CrossRefPubMedGoogle Scholar
  37. Jones, B. J., Paterson, I. A., & Roberts, M. H. T. (1986). Microinjections of methyl-b-carboline-3-carboxylate into the dorsal raphé nucleus: Behavioral consequences. Pharmacology, Biochemistry and Behavior, 24, 1487–1489.Google Scholar
  38. Kennett, G. A., Marcou, M., Dourish, C. T., & Curzon, G. (1987). Single administration of 5-HT1A agonists de crease 5-HT1A presynaptic, but not postsynaptic receptor mediated responses: Relationship to antidepressant-like actions. European Journal of Pharmacology, 138, 56–60.CrossRefGoogle Scholar
  39. LeDoux, J. E. (1995). Emotion: clues from the brain. Annual Review of Psychology, 46, 209–235.CrossRefPubMedGoogle Scholar
  40. LeDoux, J. E., Iwata, J., Cicchetti, P., & Reis, D. J. (1988). Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned ear. Journal of Neuroscience, 8, 2517–2519.PubMedGoogle Scholar
  41. Lee, R. K. K., & Maier, S. F. (1988). Inescapable shock and attention to internal versus external cues in a water escape discrimination task. Journal of Experimental Psychology: Animal Behavior Processes, 14, 302–311.CrossRefGoogle Scholar
  42. Lista, A., Blier, P., & de Montigny, C. (1990). Benzodiaze pine receptors modulate 5-HT neurotransmission in the rat hippocampus: In vivo electrophysiological evidence. Journal of Pharmacology and Experimental Therapeutics, 254, 318–323.PubMedGoogle Scholar
  43. Ma, Q. T., Yin, G. F., Ai, M. K., & Han, J. S. (1991). Serotonergic projections from the nucleus raphe dorsalis to the amygdala in the rat. Neuroscience Letters, 134, 21–24.CrossRefPubMedGoogle Scholar
  44. Maier, S. F. (1990a). Diazepam modulation of stress-induced analgesia depends on the type of analgesia. Behavioral Neuroscience, 104, 337–345.Google Scholar
  45. Maier, S. F. (1990b). The role of fear in mediating the shuttle escape learning deficit produced by inescapable shock. Journal of Experimental Psychology: Animal Behavior Processes, 16, 137–150.CrossRefGoogle Scholar
  46. Maier, S. F. (1993). Learne d helplessness, fear and anxiety. In C. Stanford & P. Salmon (Eds.), Stress: From synapse to syndrome(pp. 207–248). San Diego, CA: Academic Press.Google Scholar
  47. Maier, S. F., Busch, C. R., Maswood, S., Grahn, R. E., & Watkins, L. R. (1995). The dorsal raphe nucleus is a site of action mediating the behavioral effects of the benzodiazepine receptor inverse agonist DMCM. Behavioral Neuroscience, 109, 759–766.CrossRefPubMedGoogle Scholar
  48. Maier, S. F., Grahn, R. E., Kalman, B. A., Sutton, L. C., Wiertelak, E. P., & Watkins, L. R. (1993). The role of the amygdala and dorsal raphe nucleus in mediating the behavioral consequences of inescapable shock. Behavioral Neuroscience, 107, 377–388.CrossRefPubMedGoogle Scholar
  49. Maier, S. F., Grahn, R. E., Maswood, S., & Watkins, L. R. (1995). The benzodiaze pine receptor antagonist flumazenil and CGS8216 block the enhancement of fear conditioning 26 and interference with escape behavior produced by inescapable shock. Psychopharmacology, 121, 250–259.PubMedGoogle Scholar
  50. Maier, S. F., Grahn, R. E., & Watkins, L. R. (1995). 8-OH-DPAT microinjected in the region of the dorsal raphe nucleus blocks and reverses the enhanced fear conditioning and the interference with escape produced by exposure to inescapable shock. Behavioral Neuroscience, 109, 404–412.CrossRefPubMedGoogle Scholar
  51. Maier, S. F., Kalman, B. A., & Grahn, R. E. (1994). Chlordiazepoxide microinjected into the region of the dorsal raphe nucleus eliminates the interference with escape responding produced by inescapable shock whether administered before inescapable shock or escape testing. Behavioral Neuroscience, 108, 121–130.CrossRefPubMedGoogle Scholar
  52. Maier, S. F., & Seligman, M. E. P. (1976). Learned helplessness: Theory and evidence. Journal of Experimental Psychology: General, 105, 3–46.CrossRefGoogle Scholar
  53. Martin, I. L. (1987). The benzodiazepines and their receptors: 25 years of progress. Neuropharmacology, 26, 957–970.CrossRefPubMedGoogle Scholar
  54. Maswood, S., Barter, J. E., Watkins, L. R., & Maier, S. F. (1998). Exposure to inescapable but not escapable shock increases extracellular levels of 5-HT in the dorsal raphé nucleus of the rat. Brain Research, 783,115–120.CrossRefPubMedGoogle Scholar
  55. Matos, F. F., Urban, C., & Yocca, F. D. (1996). Serotonin (5-HT) release in the dorsal raphé and ventral hippocampus: Raphé control of somatodendritic and terminal 5-HT release. Journal of Neural Transmission, 103, 173–190.PubMedGoogle Scholar
  56. Mineka, S. (1985). Animal models of anxiety-based disorders: Their usefulness and limitations. Hillsdale, NJ: Erlbaum.Google Scholar
  57. Mineka, S., Cook, M., & Miller, S. (1984). Fear conditioned with escapable and inescapable shock: The effects of a feedback stimulus. Journal of Experimental Psychology: Animal Behavior Processes, 10, 307–323.CrossRefGoogle Scholar
  58. Mineka, S., Davidson, M., Cook, M., & Kier, R. (1984). Observational conditioning of snake fear in rhesus monkeys. Journal of Abnormal Psychology, 93, 355–372.CrossRefPubMedGoogle Scholar
  59. Minor, T. R. (1990). Conditioned fear and neophobia following inescapable shock. Animal Learning and Behavior, 18, 222–226.Google Scholar
  60. Mowrer, O. H., & Viek, P. (1948). An experimental analogue of fear from a sense of helplessness. Journal of Abnormal and Social Psychology, 83, 193–200.Google Scholar
  61. Ninan, Pe, Insel, T., Cohen, R., Cook, J., Skolnick, P., & Paul, S. M. (1982). Benzodiazepine receptor-mediated experimental “anxiety” in primates. Science, 218, 1332–1334.PubMedGoogle Scholar
  62. Pei, Q., Zetterstrom, T., & Fillenz, M. (1989). Both systemic and local administration of benzodiazepine agonists inhibit the in vivo release of 5-HT from ventral hippocampus. Neuropharmacology, 28, 1061–1066.CrossRefPubMedGoogle Scholar
  63. Peterson, C., Maier, S. F., & Seligman, M. E. P. (1993). Learned helplessness. New York: Oxford University Press.Google Scholar
  64. Petty, F., Kramer, G., Wilson, L., & Jordan, L. (1992). Prevention of learned helplessness: In vivo correlations with cortical serotonin. Psychiatric Research, 52, 285–293.CrossRefGoogle Scholar
  65. Radja, F., Laporte, A. M., Daval, G., Vergé, D., Gozlan, H., & Hamon, M. (1991). Autoradiography of serotonin receptor subtypes in the central nervous system. Neurochemistry International, 18, 1–15.CrossRefGoogle Scholar
  66. Rapaport, P. M., & Maier, S. F. (1978). Inescapable shock and food competition dominance in rats. Animal Learning and Behavior, 6, 160–165.Google Scholar
  67. Robinson, T. E., & Berridge, K. C. (1993). The neural basis of drug craving: An incentive sensitization theory of addiction. Brain Research Review, 18, 247–291.CrossRefGoogle Scholar
  68. Short, K. R., & Maier, S. F. (1993). Stressor controllability, social interaction, and benzodiazepine systems. Pharmacology, Biochemistry and Behavior, 45, 1–9.Google Scholar
  69. Steinbusch, H. M. W., & Nieuwenhuys, R. (1983). The raphé nuclei of the rat brain stem: A cytoarchitectonic and immunohistochemical study. New York: Raven Press.Google Scholar
  70. Tao, R., & Auerbach, S. B. (1994). Increased extracellular serotonin in rat brain after systemic or intraraphe administration of morphine. Journal of Neurochemistry, 63, 517–524.PubMedGoogle Scholar
  71. van der Kolk, B. A. (1988). The trauma spectrum: The interaction of biological and social events in the genesis of the trauma response. Journal of Trauma and Stress, 1, 279–290.Google Scholar
  72. Weiss, J. M., Goodman, P. A., Losito, B. G., Corrigan, S., Charry, J. M., & Bailey, W. H. (1981). Behavioral depression produced by an uncontrollable stressor: Relationship to norepinephrine, dopamine, and serotonin levels in various regions of rat brain. Brain Research, 3, 167–205.CrossRefGoogle Scholar
  73. Will, M. J., Watkins, L. R., & Maier, S. F. (1998). Uncontrollable stressors potentiate the rewarding properties of morphine. Pharmacology, Biochemistry, and Behavior, 60,655–664.Google Scholar
  74. Williams, J. L., & Groux, M. L. (1993). Exposure to various stressors alters preferences for natural odors in rats (Rattus norvegicus). Journal of Comparative Psychology, 107, 39–47.PubMedGoogle Scholar
  75. Yoshimoto, K., & McBride, W. J. (1993). Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in the rat. Neurochemical Research, 17, 401–407.Google Scholar

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© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Steven F. Maier
  • Linda R. Watkins

There are no affiliations available

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