LSD as an agonist of dopamine receptors in the striatum

Abstract

THE mechanism of the hallucinogenic action of (+)-lysergic acid diethylamide (LSD) is still obscure. Its molecular structure (containing both an indole and a phenylethylamine moiety) suggests the possibility of an interaction with brain monoamines. The earliest hypothesis postulated an antagonistic action of LSD at 5-hydroxytryptamine (5-HT) receptors in the brain1,2. More recent data rather tend to support the view that the hallucinogen mimics at least some of the effects of endogenous cerebral 5-HT3–5. Inhibition of the release of 5-HT is another suggested mechanism of action6. An interaction of LSD with dopaminergic transmission has so far not been demonstrated, although the marked attenuation of LSD-induced symptoms by chlorpromazine and other antipsychotic drugs7–9 may suggest this. Using a modification of the rotational model proposed by Ungerstedt10 we found that LSD acted as a potent agonist at dopamine receptors in the striatum.

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References

  1. 1

    Gaddum, J. H., Physiol., Lond., 121, 15P (1953). Gaddum, J. H., Br. J. Pharmac., 9, 240–248 (1954).

  2. 2

    Woolley, D. W., and Shaw, E., Proc. natn. Acad. Sci. U.S.A., 40, 228–231 (1954).

  3. 3

    Andén, N.-E., Corrodi, H., Fuxe, K., and Hökfelt, T., Br. J. Pharmac., 34, 1–7 (1968).

  4. 4

    Aghajanian, G. K., A. Rev. Pharmac., 12, 157–168 (1972).

  5. 5

    Jalfre, M., Ruch-Monachon, M. A., and Haefely, W., in Advances in Biochemical Psycho pharmacology, Vol. 10, 121–134 (Raven Press, New York, 1974).

  6. 6

    Katz, R. I., and Kopin, I. J., Pharmacol. Res. Comm., 1, 54–62 (1969).

  7. 7

    Isbell, H., and Logan, C. R., Archs Neurol. Psychiat. Chicago, 77, 350–358 (1957).

  8. 8

    Dixon, A. K., Experientia, 30, 697 (1974).

  9. 9

    Moskowitz, D., Milit. Med., 136, 754–756 (1971).

  10. 10

    Ungerstedt, U., Avemo, A., Avemo, E., Ljungberg, T., and Ranje, C., in Advances in Neurology, Vol. 3 Progress in the Treatment of Parkinsonism (edit. by Calne, D. B.), 257–271 (Raven Press, New York, 1973).

  11. 11

    Saner, A., Pieri, L., Moran, M., Da Prada, M., and Pletscher, A., Brain Res., 76, 109–117 (1974).

  12. 12

    Saner, A., Pieri, L., Da Prada, M., and Pletscher, A., Experentia, 30, 697 (1974).

  13. 13

    Roseerans, J. A., Lovell, R. A., and Freedman, D. X., Biochem. Pharmac., 16, 2011–2021 (1967).

  14. 14

    Freedman, D. X., Appel, J. B., Hartman, F. R., and Molliver, M. E., J. Pharmac. exp. Ther., 143, 309–313 (1964).

  15. 15

    Uzunov, P., and Weiss, B., in Advances in Cyclic Nucleotide Research, Vol. 1 (edit. by Greengard, P., and Robison, G. A.), 435–453 (Raven Press, New York, 1972).

  16. 16

    Rothlin, E., Ann. N. Y. Acad. Sci., 66, 668–676 (1957).

  17. 17

    Corrodi, H., Fuxe, K., Hökfelt, P., and Ungerstedt, U., J. Pharm. Pharmac., 25, 409–412 (1973).

  18. 18

    Woodruff, G. M., Elkhawad, A. O., and Crossman, A. R., Pharm. Pharmac., 26, 455–456 (1974).

  19. 19

    Thierry, A. M., Stinus, L., Blanc, G., and Glowinski, J., Brain Res., 50, 230–234 (1973).

  20. 20

    Thierry, A. M., Blanc, J., Sobel, A., Stinus, L., and Glowinski, J., Science, 182, 499–501 (1973).

  21. 21

    Hökfelt, T., Ljungdahl, Å., Fuxe, K., and Johansson, O., Science, 184, 177–179 (1974).

  22. 22

    Fuxe, K., Hökfelt, T., and Ungerstedt, U., in Symposium Bel-Air IV Monoamines noyaux gris centraux et syndrome de Parkinson (edit. by de Ajuriaguerra, J., and Gauthier, G.) 23–60 (Georg, Genève, Masson, Paris, 1971).

  23. 23

    Marczynski, T. J., Expl Neurol., 34, 255–263 (1972).

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PIERI, L., PIERI, M. & HAEFELY, W. LSD as an agonist of dopamine receptors in the striatum. Nature 252, 586–588 (1974). https://doi.org/10.1038/252586a0

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