Behavioral Pharmacology of Stress: Focus on CNS Corticotropin-Releasing Factor

  • George F. Koob
  • Karen Thatcher-Briton
  • Abdelouahhab Tazi
  • Michel Le Moal
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 245)


Stress is a hypothetical construct which has been extensively studied for the past three decades at different levels of analysis. It is a ubiquitous concept in physiology, psychology and medicine that often eludes precise definition. Hans Selye conceptualized stress as “a nonspecific response to any demand upon the body (usually, but not always, noxious), or anything which causes an alteration of homeostatic processes (1)”. A more modern version of this definition, taken from Burchfield (2) has emphasized the concept of psychological homeostasis or the maintenance of a normal mood state at rest. All emotions then are changes from this state. Indeed, as Dr. John Mason showed so elegantly, without emotional changes accompanying a stressor, the stress response is minimal (3). Thus commonly accepted physiological “stressors” (heat, excercise, hunger) do not elicit a “stress response” when they are presented in a way that eliminates their psychological (emotional) effects (fear, conflict, uncertainty, frustration).


Corticotropin Release Factor Acoustic Startle Shock Intensity Conflict Test Corticotropin Release Factor 
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  1. 1.
    H. Selye, “Selye’s guide to stress research.” Van Nostrand Reinhold Co., New York V–VIII (1980).Google Scholar
  2. 2.
    S. Burchfieldr The stress responses: a new perspective. Psychosomatic Med. 41:661–672 (1979).Google Scholar
  3. 3.
    J.W. Mason, A re-evaluation of the concept of “non-specificity” in stress specificity in stress theory. J. Psychiatric Res. 8:323–333 (1971).CrossRefGoogle Scholar
  4. 4.
    W. Vale, J. Spiess, C. Rivier, and J. Rivier, Characterization of a 41-residue ovine hypothalamic peptide that stimulates the secretion of corticotropin and β-endorphin. Science 213:1394–1397 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    L.W. Swanson, P.E. Sawchenko, J. Rivier, and W. Vale, Organization of ovine corticotropin releasing factor immunoreactive cells and fibres in the rat brain: An iitmunohistochemical study. Neuroendocrinology 36:165–186 (1983).PubMedCrossRefGoogle Scholar
  6. 6.
    M.R. Brown, L.A. Fisher, J. Rivier, J. Speiss, C. Rivier, and W. Vale, Corticotropin releasing factor: Effects on the sympathetic nervous system and oxygen consumption. Life Sci. 30:207–210 (1982).PubMedCrossRefGoogle Scholar
  7. 7.
    M.R. Brown, L.A. Fisher, J. Spiess, J. Rivier, C. Rivier, and W. Vale, Comparison of the biologic actions of corticotropin releasing factor and sauvagine. Regulatory Peptides 4:107–114 (1982).PubMedCrossRefGoogle Scholar
  8. 8.
    M.R. Brown, and L.A. Fisher, Central nervous system effects of corticotropin releasing factor in the dog. Brain Res. 280:75–79 (1983).PubMedCrossRefGoogle Scholar
  9. 9.
    C.L. Ehlers, F.E. Bloom, S.J. Henriksen, J. Rivier, and W.W. Vale, Corticotropin releasing factor produces increases in brain excitability and convulsive seizures in rats. Brain Res. 278:332–336 (1983).PubMedCrossRefGoogle Scholar
  10. 10.
    R.J. Valentino, S.L. Foote, and G. Aston-Jones, Corticotropin releasing factor activates noradrenergic neurons of the locus coeruleus. Brain Res. 270:363–367 (1983).PubMedCrossRefGoogle Scholar
  11. 11.
    R. Sutton, G.F. Koob, M. Le Moal, J. Rivier, and W. Vale, Corticotropin releasing factor (CRF) produces behavioral activation in rats. Nature 299:331–333 (1982).CrossRefGoogle Scholar
  12. 12.
    G.F. Koob, N. Swerdlow, M. Seeligson, M. Eaves, R. Sutton, J. Rivier, and W. Vale, CRF-induced locomotor activation is antagonized by alpha-flupenthixol but not by naloxone. Neuroendocrinol. 39:359–464 (1984).CrossRefGoogle Scholar
  13. 13.
    M. Eaves, K. Thatcher-Britton, J. Rivier, W. Vale, and G.F. Koob, Effects of corticotropin releasing factor on locomotor activity in hypophysectomized rats. Peptides 6:923–926 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    D.R. Britton, M. Varela, A. Garcia, and J. Rivier, Dexamethasone suppresses pituitary-adrenal but not behavioral effects of centrally administered CRF. Life Sci. 38:211–216 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    K.T. Britton, G. Lee, R. Dana, S.C. Risch, and G.F. Koob, Activating and “anxiogenic” effects of CRF are not inhibited by blockade of the pituitary-adrenal system with dexamethasone. Life Sci. 39:1281–1286 (1986).PubMedCrossRefGoogle Scholar
  16. 16.
    N.R. Swerdlow and G.F. Koob, Separate neural substrates of the locomotor-activating properties of amphetamine, heroin, caffeine, and corticotropin releasing factor (CRF) in the rat. Pharmacology, Biochemistry and Behav. 23:303–307 (1985).CrossRefGoogle Scholar
  17. 17.
    W.H. Gispen, V.M. Weigant, H.H. Greven, and D. De Wied, The induction of excessive grooming in the rat by intraventricular application of peptides derived from ACTH: structure activity. Life Sci. 17:645–655 (1975).PubMedCrossRefGoogle Scholar
  18. 18.
    D.E. Berlyne, “Conflict Arousal and Curiosity,” McGraw Hill Book Co. Inc., New York (1960).CrossRefGoogle Scholar
  19. 19.
    P.R. Killeen, S.J. Hanson, and S.R. Osbourne, Arousal: its genesis and manifestation as response rate. Psychological Rev. 85:571–581 (1978).CrossRefGoogle Scholar
  20. 20.
    J.W. Hennessy, and S. Levine, A psychoendocrine hypothesis. in: “Progress in Psychobiology and Physiological Psychology”, J.M. Sprague, A.N. Epstein, eds., Academic Press 8:133-178 (1979).Google Scholar
  21. 21.
    G.F. Koob, and F.E. Bloom, Corticotropin-releasing factor and behavior. Fed. Proc. 44:259–263 (1985).PubMedGoogle Scholar
  22. 22.
    G.N.O., Brito, G.J. Thomas, S.J. Gingold, and D.M. Gash, Behavioral characteristics of vasopressin-deficit rats (Brattleboro Strain). Brain Res. Bull. 6:71–75 (1981).PubMedCrossRefGoogle Scholar
  23. 23.
    D.R. Britton, G.F. Koob, J. Rivier, and W. Vale, Intraventricular corticotropin releasing factor enhances behavioral effects of novelty. Life Sci. 31:363–367 (1982).PubMedCrossRefGoogle Scholar
  24. 24.
    D.R. Britton and K.T. Britton, A sensitive open field measure of anxiolytic drug activity. Pharmacology, Biochemistry and Behavior 15:577–582 (1981).PubMedCrossRefGoogle Scholar
  25. 25.
    L. Cook and J. Sepinwall, Behavioral analysis of the effects and mechanism of action of benzodiazepines. in: “Mechanisms of action of benzodiazepines,” E. Costa, P. Greengard, eds., Raven Press, New York (1975).Google Scholar
  26. 26.
    K.T. Britton, J. Morgan, J. Rivier, W. Vale, and G.F. Koob, Chlordiazepoxide attenuates CRF-induced responses suppression in the conflict test. Psychopharmacology 86:170–174 (1985).PubMedCrossRefGoogle Scholar
  27. 27.
    N. Swerdlow, M. Geyer, W.W. Vale, and G.F. Koob, Cortocotropin releasing factor potentiates acoustic startle in the rats: Blockade by chlordiazepoxide. Psychopharmacol. 88:142–152 (1986).Google Scholar
  28. 28.
    A. Tazi, R. Dantzer, M. Le Moal, J. Rivier, W. Vale, and Koob, G.F. Corticotropin-releasing factor antagonist blocks stress-induced fighting in rats. Regulatory Peptides, in press (1987).Google Scholar
  29. 29.
    A. Tazi, R. Dantzer, R. Mormede, and M. Le Moal, Effects of post-trial injection of β-endorphin on shock-induced fighting are dependent on baseline of fighting. Behav. and Neural Biol. 43:322–326 (1985).CrossRefGoogle Scholar
  30. 30.
    A. Tazi, R. Dantzer, R. Mormede, and M. Le Moal, Effects of post-trial administration of naloxone and β-endorphin on shock-induced fighting in rats. Behav. and Neural Biol. 39:192–202 (1983).CrossRefGoogle Scholar
  31. 31.
    J. Rivier, C. Rivier, and W., Vale, Synthetic competitive antagonists of corticotropin-releasing factor: Effect on ACTH secretion. Science 224:889–891 (1984).PubMedCrossRefGoogle Scholar
  32. 32.
    K.T. Britton, G. Lee, W. Vale, J. Rivier, and G.F. Koob, Corticotropin releasing factor antagonists blocks activating and “anxiogenic” actions of CRF in the rat. Brain Res. 369:303–306 (1986).PubMedCrossRefGoogle Scholar
  33. 33.
    H. Selye, and G. Henser, “Fifth annual report on stress,” M.D. Publications, New York (1956).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • George F. Koob
    • 1
  • Karen Thatcher-Briton
    • 2
  • Abdelouahhab Tazi
    • 3
  • Michel Le Moal
    • 3
  1. 1.Dept of Basic and Clinical ResearchScripps Clinic and Research FoundationLa JollaUSA
  2. 2.Psychobiologie des Comportements AdaptatifsINSERM Unite-254France
  3. 3.Dept of Psychiatry, San Diego VeteransAdministration Medical Center & UCSD, Sch. of Med.La JollaUSA

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