Summary
Striatal dopamine receptors were studied using [3H]-spiperone in postmortem tissues of thirty-six patients with Parkinson's Disease. Each tissue was analyzed by the receptor saturation method. In non-treated patients, the D2 dopamine receptor density was elevated in the caudate nucleus and putamen compared to controls. In L-DOPA-treated patients, the receptor density was the same as controls. The dissociation constant for [3H]-spiperone was similar in all groups. The elevated density of D2 receptors in non-treated patients may indicate dopaminergic supersensitivity in this disease. The elevated density was reversed with dopamine agonist therapy, but the density was not lower than control tissues.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Birkmayer, W., Riederer, P.: Parkinson's Disease, p. 32. Wien-New York: Springer. 1983.
Bokobza, G., Ruberg, M., Scatton, B., Javoy-Agid, F., Agid, Y.:3H-spiperone binding, dopamine and HVA concentrations in Parkinson's Disease and supranuclear palsy. Eur. J. Pharm.99, 167–175 (1984).
Ezrin-Waters, C., Seeman, P.: L-Dopa reversal of hyperdopaminergic behaviour. Life Sci.22, 1027–1032 (1978).
Friedhoff, A., Bonnet, K., Rosengarten, H.: Reversal of two manifestations of dopamine receptor supersensitivity by administration of L-Dopa. Res. Commun. Chem. Pathol. Pharmacol.16, 411–423 (1977).
Jackson, D., Jenkins, O. F., Malor, R., Christie, M. J., Gregory, P.: Chronic L-Dopa treatment of rats and mice does not change the sensitivity of post synaptic dopamine receptors. Naunyn-Schmiedeberg's Arch. Pharmacol.324, 271–274 (1983).
Lee, T., Seeman, P., Rajput, A., Farley, I., Hornykiewicz, O.: Receptor basis for dopaminergic supersensitivity in Parkinson's disease. Nature273, 59–61 (1978).
List, S., Seeman, P.: Dopamine agonists reverse the elevated3H-neuroleptic binding in neuroleptic-pretreated rats. Life Sci.24, 1447–1452 (1979).
Olsen, R., Reisine, T., Yamamura, H.: Neurotransmitter receptors-biochemistry and alterations in neuropsychiatric disorders. Life Sci.27, 801–808 (1980).
Pycock, C., Dawbarn, D., O'Shaughnessy, C.: Behavioral and biochemical changes following chronic administration of L-Dopa to rats. Eur. J. Pharmacol.79, 201–215 (1982).
Quik, M., Spokes, E., MacKay, A., Bannister, R.: Alterations in3H-spiperone binding in human caudate nucleus, substantia nigra and frontal cortex in the Shy-Drager syndrome and Parkinson's Disease. J. Neurol. Sci.43, 429–437 (1979).
Reches, A., Wagner, H., Jackson-Lewis, V., Yablonskaya-Alter, E., Fahn, S.: Chronic levodopa or pergolide administration induces down-regulation of dopamine receptors in denervated striatum. Neurology34, 1208–1212 (1984).
Reches, A., Wagner, R., Jackson, V., Yablonskaya-Alter, E., Fahn, S.: Dopamine receptors in the denervated striatum: further supersensitivity by chronic haloperidol treatment. Brain Res.275, 183–185 (1983).
Reches, A., Wagner, H., Jiang, D., Jackson, V., Fahn, S.: The effect of chronic L-Dopa administration on supersensitive pre- and postsynaptic dopaminergic receptors in rat brain. Life Sci.31, 37–44 (1982).
Reisine, T., Fields, J., Yamamura, H.: Neurotransmitter receptor alterations in Parkinson's Disease. Life Sci.21, 335–344 (1977).
Riederer, P., Jellinger, K.: Morphologie und Pathobiochemie der Parkinson-Krankheit. In: Pathophysiologie, Klinik und Therapie des Parkinsonismus (Gänshirt, G., ed.), pp. 31–50. Basel: Roche. 1983.
Rinne, U., Rinne, J. O., Rinne, J. K., Laakso, K., Laihinen, A., Lonnberg, P.: Brain receptor changes in Parkinson's Disease in relation to the disease process and treatment. J. Neural Transm. Suppl. 18, pp. 279–286. Wien-New York: Springer. 1983.
Rinne, U.: Brain neurotransmitter receptors in Parkinson's disease. In: Movement Disorders (Marsden, C., Fahn, S., eds.), pp. 59–74. Butterworth. 1982.
Rinne, U.: Treatment of Parkinson's Disease: problems with a progressing disease. J. Neural Transm.51, 161–174 (1981 a).
Rinne, U., Lonnberg, P., Koskinen, V.: Dopamine receptors in the Parkinsonian brain. J. Neural Transm.51, 97–106 (1981 b).
Rinne, U., Koskinen, V., Lonnberg, P.: Neurotransmitter receptors in the Parkinsonian brain. In: Parkinson's Disease-Current Progress, Problems and Management (Rinne, U., Klinger, M., Stamm, G., eds), pp. 93–107. Elsevier/North-Holland Biomedical Press. 1980.
Rinne, U., Sonninen, V., Laaksonen, K.: Responses of brain neurochemistry to Levodopa treatment in Parkinson's Disease. Adv. Neurol.24, 259–274 (1979).
Schneider, M., Murrin, L., Pfeiffer, R., Deupree, J.: Dopamine receptors: effects of chronic L-Dopa and bromocriptine treatment in an animal model of Parkinson's disease. Clin. Neuropharm.7, 247–257 (1984).
Seeman, P., Ulpian, C., Wreggett, K., Wells, J.: Dopamine receptor parameters detected by3H-spiperone depend on tissue concentration: analysis and examples. J. Neurochem.43, 221–235 (1984).
Seeman, P.: Brain dopamine receptors. Pharmacol. Rev.32, 229–313 (1980).
Staunton, D., Magistretti, P., Koob, G., Shoemaker, W., Bloom, F.: Dopaminergic supersensitivity induced by denervation and chronic receptor blockade is additive. Nature299, 72–74 (1982).
Suga, M.: Effect of long-term L-DOPA administration on the dopaminergic and cholinergic (muscarinic) receptors of striatum in 6-hydroxydopamine lesioned rats. Life Sci.27, 878–883 (1980).
Winkler, M., Barl, S., Whetsell, W., Yahr, M.: Spiroperidol binding in the human caudate nucleus. J. Neural Transm.S 16, 45–51 (1980).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Guttman, M., Seeman, P. L-DOPA reverses the elevated density of D2 dopamine receptors in Parkinson's diseased striatum. J. Neural Transmission 64, 93–103 (1985). https://doi.org/10.1007/BF01245971
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01245971