Advertisement

Effects and Interactions of Imipramine, Chlorpromazine, Reserpine and Amphetamine on Self-Stimulation: Possible Neurophysiological Basis of Depression

  • Larry Stein
  • Harold E. Himwich

Abstract

Neural theorizing about the affective disorders has been given substance by recent discoveries of brain systems for positive and negative reinforcement. Brain loci for negative motivation were demonstrated by Delgado, Roberts, and Miller [1] in experiments that followed up the early work of Hess [2]. These investigators showed that electrical stimulation of certain thalamic and hippocampal sites in the cat could be substituted for painful stimulation for the motivation of several forms of learning, including the conditioning of anxiety. Shortly thereafter, Olds and Milner [3] reported that electrical stimulation of the septal region and parts of the hypothalamus had the effect of a powerful reward. This was ingeniously demonstrated by a “self-stimulation” experiment in which rats with permanent electrodes were trained to stimulate their own brains thousands of times per hour by pressing a lever. These findings have been generalized to a number of species and have been extended even to man. In the human studies, subjective reports of pleasure and pain have been obtained after electrical stimulation of specific subcortical regions [4].

Keywords

Electrical Stimulation Reward Structure Electroconvulsive Shock Reward Threshold Neurophysiological Basis 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Delgado, J. M. R., Roberts, W. W., and Miller, N. E.: Learning motivated by electrical stimulation of the brain, Am. J. Physiol. 179: 587, 1954.PubMedGoogle Scholar
  2. 2.
    Hess, W. R.: The Functional Organization of the Diencephalon, Grune and Stratton, Inc., New York, 1957.Google Scholar
  3. 3.
    Olds, J., and Milner, P.: Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain, J. Comp Physiol. Psychol. 47: 419, 1954.PubMedCrossRefGoogle Scholar
  4. 4.
    Heath, R. G., and Mickle, W. A.; Sem-Jacobsen, C. W., and Torkildsen, A.: in Ramey, E. R., and O’Doherty, D. S., Ed.: Electrical Studies onthe Unanesthetized Brain, Paul B. Hoeber, Inc., New York, 1960, chs.Google Scholar
  5. 5.
    Olds, J.: Studies of neuropharmacologicals by electrical and chemical manipulation of the brain on animals with chronically implanted electrodes, in Bradley, B. P. et al., Eds.: Neuro-Psychopharmacology, Elsevier Publ. Co., Amsterdam, 1959.Google Scholar
  6. 6.
    Olds, J., and Travis, R. P.: Effects of chlorpromazine, meprobamate, pentobarbital, and morphine on self-stimulation, J. Pharmacol. Exp. Therap. 128: 397, 1960.Google Scholar
  7. 7.
    Estes, W. K., and Skinner, B. F.: Some quantitative properties of anxiety, J. Exp. Psychol. 29: 390, 1941.CrossRefGoogle Scholar
  8. 8.
    Hunt, H. F., and Brady, J. V.: Some effects of electro-convulsive shock on a conditioned emotional response (“anxiety”), J. Comp. Physiol. Psychol. 44: 88, 1951.PubMedCrossRefGoogle Scholar
  9. 9.
    Costa, E., Garattini, S., and Valzelli, L.: Interactions between reserpine, chlorpromazine, and imipramine, Experientia 16: 461, 1960.PubMedCrossRefGoogle Scholar
  10. 10.
    Lilly, J. C., Hughes, J. R., Alvord, E. C., Jr., and Galken, T. W.: Brief non-injurious electrical waveform for stimulation of the brain, Science 121: 468, 1955.PubMedCrossRefGoogle Scholar
  11. 11.
    Brodie, D. A., Moreno, D. M., Malis, J. L., and Boren, J. J.: Rewardingproperties of intercranial stimulation, ibid. 131: 929, 1960.Google Scholar
  12. 12.
    Stein, L., and Ray, O. S.: Brain stimulation reward “thresholds” self-determined in rat, Psychopharmacologia 1: 251, 1960.PubMedCrossRefGoogle Scholar
  13. 13.
    Sigg, E. B.: Pharmacological studies with Tofranil, Canadian Psychiat. Assoc. J. 4: 575, 1959.Google Scholar
  14. 14.
    Carlton, P. L.: Augmentation of the behavioral effects of amphetamine by atropine, Pharmacologist 2: 70, 1960.Google Scholar
  15. 15.
    Stein, L.: Secondary reinforcement established with subcortical stimulation, Science 127: 466, 1958.PubMedCrossRefGoogle Scholar
  16. 16.
    Martin, W. R., Riehl, J. L., and Unna, K. R.: Chlorpromazine III. The effects of chlorpromazine and chlorpromazine sulfoxide on vascular responses to 1-epinephrine and levarterenol, J. Pharmacol. Exp. Therap. 130: 37, 1960.Google Scholar
  17. 17.
    Vogt, M.: The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs, J. Physiol. 123: 451, 1954.PubMedGoogle Scholar
  18. 18.
    Brodie, B. B., and Shore, P. A.: A concept for a role of serotonin and norepinephrine as chemical mediators in the brain, Ann. N. Y. Acad. Sci. 66: 631, 1957.PubMedCrossRefGoogle Scholar
  19. 19.
    Stein, L.: New methods for evaluating stimulants and antidepressants, in Nodine, J. H., Ed.: Sixth Hahnemann Symposium: Psychosomatic Medicine, Lea and Febiger, 1962.Google Scholar
  20. 20.
    Goldstein, M. and Contrera, J F • Inhibition of dopamine ß -oxidase by imipramine, Biochem. Pharmacol. 7: 278, 1961.Google Scholar
  21. 21.
    Axelrod, J.: Metabolism of epinephrine and other sympathomimetic amines, Physiol. Rev. 39: 751, 1959.Google Scholar

Copyright information

© Plenum Press Inc. 1962

Authors and Affiliations

  • Larry Stein
  • Harold E. Himwich

There are no affiliations available

Personalised recommendations