Serotonergic and cholinergic mechanisms during disruption of approach and avoidance behavior

  • M. H. Aprison
  • J. N. Hingtgen
  • W. J. McBride
Part of the FASEB Monographs book series (FASEBM, volume 4)


Injections of d,l-5-hydroxytryptophan (d,l-5-HTP) into pigeons and rats’ working on approach schedules produce a period of behavioral depression that is temporally correlated to increased levels of total serotonin (5-HT) in the telencephalon and diencephalon. Administration of α-methyl-meta-tyrosine (α-MMT) also results in depressed responding; however, the temporal correlation is with decreased levels of total 5-HT in brain. Our hypothesis to explain these two apparent opposite biochemical states which result in similar behavioral disruptions is that in both cases more 5-HT is released within certain key serotonergic synapses mediating this behavior. Evidence from subcellular studies supports this concept. Not only are the levels of 5-HT significantly higher in preparations of nerve endings isolated from the telencephalon and diencephalon of pigeons given injections of d,l-5-HTP, but in vitro studies also show that low concentrations of l-5-HTP significantly increased the release of radioactive 5-HT from serotonergic nerve endings. On the other hand, l-5-HTP in much higher concentrations had no effect on the release of labeled dopamine or norephinephrine. A major metabolite of α-MMT, α-methyl-meta-tyramine, also caused a significant increase in the release of labeled 5-HT from similar preparations of nerve endings. Whereas serotonin appears to be involved in the disruption of approach behavior, another series of studies have indicated that acetylcholine may play a role in excitation during avoidance behavior. Behavioral excitation observed following administration of tetrabenazine 18 hr after iproniazid pretreatment to rats working on shock-avoidance schedules was temporally correlated with lowered levels of acetylcholine in the telencephalon. Pretreatment with 0.8 mg/kg of atropine blocked excitation whereas one-eighth of this dose increased the duration. Excitation in these rats was shortened by 50% following bilateral septal lesions, which lowered brain acetylcholine levels. Mechanisms to explain these neurochemical correlates of behavior are discussed.—Aprison, M. H., J. N. Hingtgen, and W. J. Mcbride. Serotonergic and cholinergic mechanisms during disruption of approach and avoidance behavior. Federation Proc. 34: 1813–1822, 1975.


Nerve Ending Avoidance Behavior Optic Lobe Approach Behavior Brain Part 
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.







5-hydroxytryptamine (serotonin)


5-hydroxyindole-acetic acid


monamine oxidase




dopamine (3,4-dihydroxyphenylethylamine)













Mult FR 50 FI 10

multiple fixed-ratio 50, fixed-interval 10 minutes.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aprison, M. H. J. Neurochem. 2: 197, 1958.PubMedCrossRefGoogle Scholar
  2. 2.
    Aprison, M. H. Recent Ad. Biol. Psychiatry 4: 133, 1962.CrossRefGoogle Scholar
  3. 3.
    Aprison, M. H., and C. B. Ferster. Experientia 16: 159, 1960.PubMedCrossRefGoogle Scholar
  4. 4.
    Aprison, M. H., and C. B. Ferster. J. Neurochem. 6: 350, 1961.PubMedCrossRefGoogle Scholar
  5. 5.
    Aprison, M. H., and C. B. Ferster. J. Pharmacol. Exp. Ther. 131: 100, 1961.PubMedGoogle Scholar
  6. 6.
    Aprison, M. H., and J. N. Hingtgen. J. Neurochem. 12: 959, 1965.PubMedCrossRefGoogle Scholar
  7. 7.
    Aprison, M. H., and J. N. Hingtgen. Life Sci. 5: 1971, 1966.Google Scholar
  8. 8.
    Aprison, M. H., and J. N. Hingtgen. Recent Adv. Biol. Psychiatry 8: 87, 1966.Google Scholar
  9. 9.
    Aprison, M. H., and J. N. Hingtgen. Biol. Psychiatry 1: 87, 1969.PubMedGoogle Scholar
  10. 10.
    Aprison, M. H., and J. N. Hingtgen. Int. Rev. Neurobiol. 13: 325, 1970.CrossRefGoogle Scholar
  11. 11.
    Aprison, M. H., and J. N. Hingtgen. Federation Proc. 31: 121, 1972.Google Scholar
  12. 12.
    Aprison, M. H., T. Kariya, J. N. Hingtgen and M. Toru. J. Neurochem. 15: 1131, 1968.PubMedCrossRefGoogle Scholar
  13. 13.
    Aprison, M. H., M. A. Wolf, G. J. Poulos and T. L. Folkerth. J. Neurochem. 9: 575, 1962.PubMedCrossRefGoogle Scholar
  14. 14.
    Elliott, K. A. C., and N. Henderson. Am. J. Physiol. 165: 365, 1951.PubMedGoogle Scholar
  15. 15.
    Gessa, G. L., E. Costa, R. Kuntzman and B. B. Brodie. Life Sci. 1: 353, 1962.PubMedCrossRefGoogle Scholar
  16. 16.
    Hingtgen, J. N., and M. H. Aprison. Science 141: 169, 1963.PubMedCrossRefGoogle Scholar
  17. 17.
    Hingtgen, J. N., and M. H. Aprison. Life Sci. 5: 1249, 1966.CrossRefGoogle Scholar
  18. 18.
    Hingtgen, J. N., and M. H. Aprison. Neuropharmacology 9: 419, 1970.PubMedCrossRefGoogle Scholar
  19. 19.
    Hingtgen, J. N., M. H. Aprison, W. C. Black and J. C. Sloan. Experientia 29: 74, 1973.PubMedCrossRefGoogle Scholar
  20. 19a.
    Hingtgen, J. N., and M. H. Aprison. Life Sci. In press.Google Scholar
  21. 20.
    Liang, C. C., and J. H. Quastel. Biochem. Pharmacol. 18: 1187, 1969.CrossRefGoogle Scholar
  22. 21.
    Mcbride, W. J., and M. H. Aprison. Pharmacol. Biochem. Behav. 1: 587, 1973.PubMedCrossRefGoogle Scholar
  23. 22.
    Mcbride, W. J., M. H. Aprison and J. N. Hlngtgen. Neuropharmacology 12: 769, 1973.PubMedCrossRefGoogle Scholar
  24. 23.
    Mcbride, W. J., M. H. Aprison and J. N. Hlngtgen. J. Neurochem. 23: 385, 1974.PubMedCrossRefGoogle Scholar
  25. 24.
    Pepeu, G., A. Mulas, A. Ruff and P. Sotgiu. Life Sci. 10: 181, 1971.CrossRefGoogle Scholar
  26. 25.
    Polak, R. L., and M. W. Meeuws. Biochem. Pharmacol. 15: 989, 1966.PubMedCrossRefGoogle Scholar
  27. 26.
    Porter, C. C., J. A. Totaro and C. M. Leibyj. Pharmacol Exp. Ther. 134: 139, 1961.Google Scholar
  28. 27.
    Schuberth, J., and A. Sundwall. J. Neurochem. 14: 807, 1967.CrossRefGoogle Scholar
  29. 28.
    Shore, P. A., D. Busfield and H. S. Alpers. J. Pharmacol. Exp. Ther. 146: 194, 1964.PubMedGoogle Scholar
  30. 29.
    Sorensen, J. P., and J. A. Harvey. Physiol. Behav. 6: 723, 1971.PubMedCrossRefGoogle Scholar
  31. 30.
    Takahashi, R., and M. H. Aprison. J. Neurochem. 11: 887, 1964.PubMedCrossRefGoogle Scholar
  32. 31.
    Toru, M., J. N. Hlngtgen and M. H. Aprison. Life Sci. 5: 181, 1966.PubMedCrossRefGoogle Scholar
  33. 32.
    Udenfriend, S., and P. Zaltzmannirenberg. J. Pharmacol. Exp. Ther. 138: 194, 1962.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1975

Authors and Affiliations

  • M. H. Aprison
    • 1
    • 2
    • 3
    • 4
  • J. N. Hingtgen
    • 1
    • 2
    • 3
    • 4
  • W. J. McBride
    • 1
    • 2
    • 3
    • 4
  1. 1.Section of NeurobiologyIndiana University Medical CenterIndianapolisUSA
  2. 2.The Institute of Psychiatric ResearchIndiana University Medical CenterIndianapolisUSA
  3. 3.Department of PsychiatryIndiana University Medical CenterIndianapolisUSA
  4. 4.Department of BiochemistryIndiana University Medical CenterIndianapolisUSA

Personalised recommendations