Psychopharmacology

, Volume 101, Issue 3, pp 366–370 | Cite as

Central effects of corticotropin releasing factor (CRF): evidence for similar interactions with environmental novelty and with caffeine

  • Donald R. Britton
  • Elzbieta Indyk
Original Investigations

Abstract

Centrally administered rat/human corticotropin-releasing factor (rCRF) increases low levels of locomotor activity by rats tested in a familiar environment but suppresses the higher levels of activity associated with exposure of the animals to a novel environment. These opposing responses do not appear to be manifestations of a simple rate-dependent effect, since ICV-administered rCRF did not lower the higher levels of locomotor activity associated with the dark (active) phase of the animal's activity cycle. Caffeine, which has anxiogenic effects in man, produces effects in rats which are similar to those of rCRF. That is, both compounds elevate activity in a familiar environment but lower activity in a novel environment. Furthermore, caffeine appears to substitute for novelty in determining the direction of the locomotor effect of rCRF. Animals made hyperactive by caffeine show decreased activity when co-administered rCRF. These findings are consistent with the view that CRF acts through pathways which also subserve the responsiveness to novelty and to the anxiogenic compound caffeine.

Key words

CRF Locomotor activity Caffeine Stress Animal models of anxiety 

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References

  1. Baldvin HA, File SE (1989) Caffeine-induced anxiogenesis: the role of adenosine, benzodiazepine and noradrenergic receptors. Pharmacol Biochem Behav 32:181–186CrossRefPubMedGoogle Scholar
  2. Berridge CW, Dunn A (1986) Corticotropin-releasing factor elicits naloxone sensitive stress-like alterations in exploratory behavior in mice. Regul Pept 16:83–93CrossRefPubMedGoogle Scholar
  3. Bloom FE, Battenberg ELF, Rivier J, Vale WW (1982) Corticotropin releasing factor (CRF): immunoreactive neurons and fibers in rat hypothalamus. Regul Pept 4:43–48CrossRefPubMedGoogle Scholar
  4. Britton DR, Britton KT (1981) A sensitive open field measure of anxiolytic drug activity. Pharmacol Biochem Behav 15:577–582CrossRefPubMedGoogle Scholar
  5. Britton DR, Indyk E (1989) Effects of ganglionic blocking agents on behavioral responses to centrally administered CRF. Brain Res 478:205–210CrossRefPubMedGoogle Scholar
  6. Britton DR, Koob GF, Rivier J, Vale W (1982) Intraventricular corticotropin-releasing factor enhances behavioral effects of novelty. Life Sci 31:363–367CrossRefPubMedGoogle Scholar
  7. Britton DR, Hoffman D, Lederis K, Rivier J (1984) A comparison of the behavioral effects of CRF, sauvagine and urotensin I. Brain Res 304:201–205CrossRefPubMedGoogle Scholar
  8. Britton DR, Varela M, Garcia A, Rosenthal M (1986) Dexamethasone suppresses pituitary-adrenal but not behavioral effects of centrally administered CRF. Life Sci 8:211–216CrossRefGoogle Scholar
  9. Britton KT, Morgan J, Rivier J, Vale W, Koob G (1985) Chlordiazepoxide attenuates CRF-induced response suppression in the conflict test. Psychopharmacology 86:107–174CrossRefGoogle Scholar
  10. Brown MR, Fisher LA, Spiess J, Rivier C, Rivier J, Vale W (1982) Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology 111:928–931PubMedGoogle Scholar
  11. Charney DS, Galloway MP, Heninger GR (1984) The effects of caffeine on plasma MHPG, subjective anxiety, autonomic symptoms and blood pressure in healthy humans. Life Sci 35:135–144CrossRefPubMedGoogle Scholar
  12. De Souza E, Insel TR, Perrin MH, Rivier J, Vale WW, Kuhar MJ (1985) Corticotropin releasing factor receptors are widely distributed within the rat central nervous system: an autoradiographic study. J Neurosci 5:3189–3203PubMedGoogle Scholar
  13. Dunn A, File S (1987) Corticotropin releasing factor has anxiogenic actions in the social interaction test. Horm Behav 21:193–202CrossRefPubMedGoogle Scholar
  14. Ehlers CL, Henriksen SJ, Wang M, Rivier J, Vale WW, Bloom FE (1983) Corticotropin releasing factor produces increases in brain excitability and convulsive seizures in rats. Brain Res 278:332–336CrossRefPubMedGoogle Scholar
  15. Fisher LA, Rivier J, Rivier C, Spiess J, Vale W, Brown MR (1982) Corticotropin-releasing factor (CRF): central effects on mean arterial pressure and heart rate in rats. Endocrinology 110:2222–2224PubMedGoogle Scholar
  16. Gosnell BA, Morley JE, Levine AS (1983) Adrenal modulation of the inhibitory effect of corticotropin releasing factor on feeding. Peptides 4:807–812CrossRefPubMedGoogle Scholar
  17. Lader M, Bruce M (1986) States of anxiety and their induction by drugs. Br J Clin Pharmacol 22:251–261PubMedGoogle Scholar
  18. Lee EHY, Tang YP, Chai CY (1987) Stress and corticotropin releasing factor potentiate center region activity of mice in an open field. Psychopharmacology 93:320–323CrossRefPubMedGoogle Scholar
  19. Lister RG (1987) The use of a plus maze to measure anxiety in the mouse. Psychopharmacology 92:180–185PubMedGoogle Scholar
  20. Morley J, Levine AS (1982) Corticotropin-releasing factor, grooming and ingestive behavior, Life Sci 31:1459–1464CrossRefPubMedGoogle Scholar
  21. Nemeroff CB, Widerlov E, Bissette G, Walleus H, Karlsson I, Eklund K, Kilts CD, Loosen PT, Vale W (1984) Elevated concentrations of corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226:1342–1344Google Scholar
  22. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167CrossRefPubMedGoogle Scholar
  23. Polc P, Bonetti EP, Pieri L, Cumin R, Angioi RM, Mohler H, Haefely WE (1981) Caffeine antagonizes several central effects of diazepam. Life Sci 28:2265–2275CrossRefPubMedGoogle Scholar
  24. Rivier C, Brownstein M, Spiess J, Rivier J, Vale W (1982) In vivo corticotropin releasing factor-induced secretion of adrenocorticotropin, beta-endorphin and corticosterone. Endocrinology 110:272–278PubMedGoogle Scholar
  25. Sherman JE, Kalin NH (1987) The effects of ICV-CRH on novelty-induced behavior. Pharmacol Biochem Behav 26:699–703CrossRefPubMedGoogle Scholar
  26. Smith MA, Bissette G, Slotkin TA, Knight DL, Nemeroff CB (1986) Release of corticotropin-releasing factor from rat brain regions in vitro. Endocrinology 118:1997–2001PubMedGoogle Scholar
  27. Sutton RE, Koob GF, LeMoal M, Rivier J, Vale W (1982) Corticotropin-releasing factor produces behavioral activation in rats. Nature 297:331–333CrossRefPubMedGoogle Scholar
  28. Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36:165–186PubMedGoogle Scholar
  29. Swerdlow NR, Koob GF (1985) Separate neural substrates of the locomotor activating properties of amphetamine, heroin, caffeine and corticotropin releasing factor (CRF) in the rat. Pharmacol Biochem Behav 23:303–307Google Scholar
  30. Swerdlow NR, Geyer MA, Vale WW, Koob GF (1986) Corticotropinreleasing factor potentiates acoustic startle in rats: blockade by chlordiazepoxide. Psychopharmacology 88:147–152CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Donald R. Britton
    • 1
    • 2
  • Elzbieta Indyk
    • 1
  1. 1.Department of Pharmacology and Molecular BiologyUniversity of the Health Sciences / Chicago Medical SchoolNorth ChicagoUSA
  2. 2.Neuroscience Research (47U), Pharmaceutical Discovery Division Abbott LaboratoriesAbbott ParkUSA

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