The Influences of ACTH 4–9 Analog upon Avoidance Learning in Normal and Brain Damaged Rats

  • W. F. McDaniel
  • M. S. Schmidt
  • F. I. Chirino Barcelo
  • B. K. Davis
Part of the Advances in Behavioral Biology book series (ABBI, volume 36)


The potential benefits of exogenous administration of the adrenocorticotropic hormone (ACTH) and some of its fragments following nervous system damage has been examined sporadically over the past 40 years. Early research (e.g., 1) reported that administration of ACTH resulted in limited functional recovery in some animals after spinal cord damage, and these beneficial effects seemed to be associated with administration shortly after the injury. Strand and Kung (2) found that ACTH accelerated the rate of nerve regeneration following nerve crush in adrenalectomized animals and concluded that ACTH stimulated an increase in protein and RNA synthesis in spinal motor neurons. Strand and Smith (3) have hypothesized that this enhanced protein synthesis results in increased synthesis and/or delivery of neurotransmitters or neurotrophic substances to sprouting axons. Similarly, it has been reported (4,5) that ACTH 1–39 facilitates functional reorganization of motor units and hastens functional recovery following either peroneal or sciatic nerve crush. Bijlsma and colleagues (6) concluded that the 4–10 amino acid sequence of ACTH was responsible for the hormone’s beneficial action on peripheral nerve regeneration and accelerated recovery of a foot-flick response. In a test of this hypothesis, these researchers repeated their earlier methodology, again using animals with crushed sciatic nerves, and found that treatment with ACTH 4–10 resulted in a striking increase in the number of myelinated axons throughout the regeneration process. Treatment with the 11–24 fragment of ACTH produced no beneficial effects. This observation has been replicated recently (7) with both fiber density and regeneration rate facilitated by ACTH 4–10 following sciatic nerve crush. Since the 4–10 (and 4–9) sequence of the hormone fails to exert an endocrine effect upon the adrenal cortex (8), it has been concluded that the facilitated nerve regeneration is independent of the corticotropic (or peripheral) influences of the hormone (6).


Retrograde Amnesia Sciatic Nerve Crush Nervous System Damage Session Block Passive Avoidance Behavior 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    McMasters, R. E. (1962) Regeneration of the spinal cord in the rat. Effects of piromen and ACTH upon the regenerative capacity. J. Comp. Neurol. 119: 113–125.CrossRefGoogle Scholar
  2. 2.
    Strand, F. L., and Kung, T. T. (1980) ACTH accelerates recovery of neuromuscular function following crushing of peripheral nerve. Peptides 1: 135–138.CrossRefGoogle Scholar
  3. 3.
    Strand, F. L., Smith, C. M. (1980) LPH, ACTH, MSH, and motor systems. Pharmacol. Ther. 11: 509–533.CrossRefGoogle Scholar
  4. 4.
    Saint-Come, C., Acker, G. R., and Strand, F. L. (1982) Peptide influences on the development and regeneration of motor performance. Peptides 3: 439–449.CrossRefGoogle Scholar
  5. 5.
    Bijlsma, W. A., Jennekens, F. G. I., Schotman, P., and Gispen, W. H. (1981) Effects of corticotrophin (ACTH) on recovery of sensorimotor function in the rat: Structure-activity study. Eur. J. Pharmac. 76: 73–79.CrossRefGoogle Scholar
  6. 6.
    Bijlsma-, W. A., Jennekens, F. G. I., Schotman, P., and Gispen, W. H. (1983) Stimulation by ACTH 4–10 of nerve fiber regeneration following sciatic nerve crush. Muscle Nerve 6: 102–110.Google Scholar
  7. 7.
    Girlanda, P., Muglia, U., Vita, G., Dattola, R., Santoro, M., Toscano, A., Venuto, C., Roberto, M. L., Baradello, A., Romano, M., and Messina, C. (1988) Effect of ACTH 4–10 on nerve fiber regeneration after sciatic nerve crush in rabbits: an electrophysiological and morphological study. Exp. Neurol. 99: 454–460.CrossRefGoogle Scholar
  8. 8.
    DeWied, D. (1980) Hormonal influences on motivation, learning, memory, and psychosis. In D. T. Krieger and J. C. Hughes (eds.), Neuroendocrinology, Sutherland, MA: Sinauer Associates, Inc., 194–204.Google Scholar
  9. 9.
    Bush, D. F., Lovely, R. H., and Pagano, R. R. (1973) Injection of ACTH induces recovery from shuttle-box avoidance deficits in rats with amygdaloid lesions. J. Comp. Physiol. Psychol. 83: 168–172.CrossRefGoogle Scholar
  10. 10.
    Isaacson, R. L., and Poplawsky, A. (1983) An ACTH 4–9 analog (ORG 2766) speeds recovery from septal hyperemotionality in the rat. Behay. Neural Biol. 39: 52–59.CrossRefGoogle Scholar
  11. 11.
    Isaacson, R. L., and Poplawsky, A. (1985) ACTH 4–10 produces a transient decrease in septal hyperemotionality. Behay. Neural Biol. 43: 109–113.CrossRefGoogle Scholar
  12. 12.
    Veldhuis, H. D., Nyakas, C., and DeWied, D. (1985) Neuropeptides and functional recovery after brain damage. In B. E. Will, P. Schmitt, and J. C. Dalrymple-Alford (eds.), Brain Plasticity, Learning, and Memory, New York: Plenum Press, 473–480.Google Scholar
  13. 13.
    Rigter, H., Veldhuis, H. D., and deKloet, E. R. (1984) Spatial learning and the hippocampal corticosterone receptor system of old rats: effect of the ACTH 4–9 analogue ORG 2766. Brain Res. 309: 393–398.CrossRefGoogle Scholar
  14. 14.
    Spruijt, B. M., Rombouts, L., and Gispen, W. H. (1987) Effects of ACTH (4–9) on behavioral plasticity in aging animals. New Trends in Aging Research (Abstract Book), Italian Study Group on Brain Aging, International Symposium, April 12–15, Sirmione, Italy, 28.Google Scholar
  15. 15.
    Walker, B. B., and Sandman, C. A. (1979) Influences of an analog of the neuropeptide ACTH 4–9 on mentally retarded adults. Am. J. Ment. Defic. 83: 346–352.Google Scholar
  16. 16.
    Fekete, M., Van Ree, J. M., and DeWied, D. (1986) The ACTH-(4–9) analog ORG 2766 and desglycinamide 9-(Arg8)-vasopressin reverse the retrograde amnesia induced by disrupting circadian rhythms in rats. Peptides 7: 563–568.CrossRefGoogle Scholar
  17. 17.
    Rigter, H. H., Van Riezen, H., and DeWied, D. (1974) The effect of ACTH-and vasopressin analogues on CO2-induced retrograde amnesia in rats. Physiol. Behay. 13: 381–388.CrossRefGoogle Scholar
  18. 18.
    de Wied, D., and van Ree, J. M. (1982) Neuropeptides, mental performance and aging. Life Sci. 31: 709–719.CrossRefGoogle Scholar
  19. 19.
    Krieger, D. T. (1983) Brain peptides: what, where, and why? Science 22: 975–985.CrossRefGoogle Scholar
  20. 20.
    McDaniel, W. F. (1985) Functions of the posterior neocortex of the rat. IRCS J. Med. Sci. 13: 286–289.Google Scholar
  21. 21.
    McDaniel, W. F., Davall, E. J., and Walker, P. E. ACTH 4–9 analog can retard spatial alternation learning in brain damaged and normal rats. Behay. Neural Biol. (in press).Google Scholar
  22. 22.
    McDaniel, W. F., and Wall, T. T. (1988) Visuospatial functions in the rat following injuries to striate, peristriate, and parietal neocortical sites. Psychobiol. 16: 251–260.Google Scholar
  23. 23.
    Kolb, B. (1984) Functions of the frontal cortex of the rat: a comparative review. Brain Res. Rev. 8: 65–98.CrossRefGoogle Scholar
  24. 24.
    Kolb, B., Sutherland, R. J., and Whishaw, I. Q. (1983) A comparison of the contributions of the frontal and parietal association cortex to spatial localization in rats. Behay. Neurosci. 97: 13–27.CrossRefGoogle Scholar
  25. 25.
    Kolb, B., and Walkey, J. (1987) Behavioural and anatomical studies of the posterior parietal cortex in the rat. Behay. Brain Res. 23: 127–145.CrossRefGoogle Scholar
  26. 26.
    Johnston, M.V., McKinney, M. and Coyle, J.T. (1981) Neocortical cholinergic innervation: a description of extrinsic and intrinsic components in the rat. Exp. Brain Res. 43: 159–172.CrossRefGoogle Scholar
  27. 27.
    Bartus, R.T., Dean, R. L., Beer, B. and Lippa, A.S. (1982) TheGoogle Scholar
  28. cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–416.Google Scholar
  29. 28.
    Arendash, G.W., Millard, W.J., Dunn, A.J., and Meyer, E.M. (1987) Longterm neuropathological and neurochemical effects of nucleus basalis lesions in the rat. Science 238: 952–956.Google Scholar
  30. 29.
    Verhoef, J., and Witter, A. (1976) In vivo fate of a behaviorally active ACTH 4–9 analog in rats after systemic administration. Pharmacol. Biochem. Behay. 4: 583–590.CrossRefGoogle Scholar
  31. 30.
    Fekete, M., and DeWied, D. (1982) Potency and duration of action of the ACTH 4–9 analog (ORG 2766) as compared to ACTH 4–10 on active and passive avoidance behavior of rats. Pharmacol. Biochem. Behay. 16: 387–392.CrossRefGoogle Scholar
  32. 31.
    Born, J., Fehm, H.L., and Voigt, K.H. (1986) ACTH and attention in humans: a review. Neuropsychobiol. 15: 165–186.CrossRefGoogle Scholar
  33. 32.
    Van Wimersma Greidanus, T.B., Bohus, B., Kovacs, G.L., Versteeg, D.H.G., Burbach, J.P.H., and DeWied, D. (1983) Sites of behavioral and neurochemical action of ACTH-like peptides and neurohypophyseal hormones. Neurosci. Biobehay. Rev. 7: 453–463.CrossRefGoogle Scholar
  34. 33.
    Passingham, R.E., Meyers, C., Rawlins, N., Lightfoot, V., and Fearn, S., (1988) Premotor cortex in the rat. Behay. Neurosci. 102: 101–109.CrossRefGoogle Scholar
  35. 34.
    Arendash, G.W., Strong, P.N., and Mouton, P.R. (1985) Intracerebral transplantation of cholinergic n-eurons in a new animal model for Alzheimer’s disease. In: Senile Dementia of the Alzheimer Type (eds: Hutton, J.T. and Kenney, A.D. ), Alan R. Liss, Inc., New York, 351–376.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • W. F. McDaniel
    • 1
  • M. S. Schmidt
    • 1
  • F. I. Chirino Barcelo
    • 1
  • B. K. Davis
    • 1
  1. 1.Department of PsychologyGeorgia CollegeMilledgevilleUSA

Personalised recommendations