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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Gaddum, J. H., Physiol., Lond., 121, 15P (1953). Gaddum, J. H., Br. J. Pharmac., 9, 240–248 (1954).
Woolley, D. W., and Shaw, E., Proc. natn. Acad. Sci. U.S.A., 40, 228–231 (1954).
Andén, N.-E., Corrodi, H., Fuxe, K., and Hökfelt, T., Br. J. Pharmac., 34, 1–7 (1968).
Aghajanian, G. K., A. Rev. Pharmac., 12, 157–168 (1972).
Jalfre, M., Ruch-Monachon, M. A., and Haefely, W., in Advances in Biochemical Psycho pharmacology, Vol. 10, 121–134 (Raven Press, New York, 1974).
Katz, R. I., and Kopin, I. J., Pharmacol. Res. Comm., 1, 54–62 (1969).
Isbell, H., and Logan, C. R., Archs Neurol. Psychiat. Chicago, 77, 350–358 (1957).
Dixon, A. K., Experientia, 30, 697 (1974).
Moskowitz, D., Milit. Med., 136, 754–756 (1971).
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).
Saner, A., Pieri, L., Moran, M., Da Prada, M., and Pletscher, A., Brain Res., 76, 109–117 (1974).
Saner, A., Pieri, L., Da Prada, M., and Pletscher, A., Experentia, 30, 697 (1974).
Roseerans, J. A., Lovell, R. A., and Freedman, D. X., Biochem. Pharmac., 16, 2011–2021 (1967).
Freedman, D. X., Appel, J. B., Hartman, F. R., and Molliver, M. E., J. Pharmac. exp. Ther., 143, 309–313 (1964).
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).
Rothlin, E., Ann. N. Y. Acad. Sci., 66, 668–676 (1957).
Corrodi, H., Fuxe, K., Hökfelt, P., and Ungerstedt, U., J. Pharm. Pharmac., 25, 409–412 (1973).
Woodruff, G. M., Elkhawad, A. O., and Crossman, A. R., Pharm. Pharmac., 26, 455–456 (1974).
Thierry, A. M., Stinus, L., Blanc, G., and Glowinski, J., Brain Res., 50, 230–234 (1973).
Thierry, A. M., Blanc, J., Sobel, A., Stinus, L., and Glowinski, J., Science, 182, 499–501 (1973).
Hökfelt, T., Ljungdahl, Å., Fuxe, K., and Johansson, O., Science, 184, 177–179 (1974).
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).
Marczynski, T. J., Expl Neurol., 34, 255–263 (1972).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1038/252586a0
This article is cited by
-
Low doses of LSD reduce broadband oscillatory power and modulate event-related potentials in healthy adults
Psychopharmacology (2022)
-
LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors
Psychopharmacology (1995)
-
Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat
Journal of Neural Transmission (1985)
-
Training dose as a factor in LSD-saline discrimination
Psychopharmacology (1982)
-
Psilocybin as a discriminative stimulus: Lack of specificity in an animal behavior model for ?hallucinogens?
Psychopharmacology (1982)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
