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Science 7 December 1990:
Vol. 250. no. 4986, pp. 1429 - 1432
DOI: 10.1126/science.2147780
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Articles

Science, Vol 250, Issue 4986, 1429-1432
Copyright © 1990 by American Association for the Advancement of Science

articles

D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons

CR Gerfen, TM Engber, LC Mahan, Z Susel, TN Chase, FJ Monsma Jr, and DR Sibley

Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892.

The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.


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Effects of Dopamine D1-like and D2-like Agonists in Rats that Self-Administer Cocaine.
S. B. Caine, S. S. Negus, N. K. Mello, and J. Bergman (1999)
J. Pharmacol. Exp. Ther. 291, 353-360
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D2 dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons.
Z. Yan, J. Feng, A. A. Fienberg, and P. Greengard (1999)
PNAS 96, 11607-11612
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Modulation of Neurotransmitter Release in the Basal Ganglia of the Rat Brain by Dynorphin Peptides.
Z.-B. You, M. Herrera-Marschitz, and L. Terenius (1999)
J. Pharmacol. Exp. Ther. 290, 1307-1315
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Drugs of Abuse and Brain Gene Expression.
G. Torres and J. M. Horowitz (1999)
Psychosom Med 61, 630-650
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