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The Journal of Neuroscience, July 15, 1998, 18(14):5301-5310
A Complex Program of Striatal Gene Expression Induced by
Dopaminergic Stimulation
Joshua D.
Berke1, 2,
Ronald F.
Paletzki3,
Gabriel J.
Aronson3,
Steven
E.
Hyman1, and
Charles R.
Gerfen3
1 Molecular Plasticity Section, National Institute of
Neurological Disorders and Stroke, Bethesda, Maryland 20892, 2 Program in Neuroscience, Harvard University, Boston,
Massachusetts 02115, and 3 Laboratory of Systems
Neuroscience, National Institute of Mental Health, Bethesda, Maryland
20892
Dopamine acting in the striatum is necessary for normal movement
and motivation. Drugs that change striatal dopamine neurotransmission can have long-term effects on striatal physiology and behavior; these
effects are thought to involve alterations in gene expression. Using
the 6-hydroxydopamine lesion model of Parkinson's disease and
differential display PCR, we have identified a set of more than 30 genes whose expression rapidly increases in response to stimulation of
striatal dopamine D1 receptors. The induced mRNAs include
both novel and previously described genes, with diverse time courses of
expression. Some genes are expressed at near-maximal levels within 30 min, whereas others show no substantial induction until 2 hr or more
after stimulation. Some of the induced genes, such as CREM, CHOP, and
MAP kinase phosphatase-1, may be components of a homeostatic response
to excessive stimulation. Others may be part of a genetic program
involved in cellular and synaptic plasticity. A very similar set of
genes is induced in unlesioned animals by administration of the
psychostimulant cocaine or the antipsychotic eticlopride, although in
distinct striatal cell populations. In contrast to some previously
described early genes, most of the novel genes are not induced in
cortex by apomorphine, indicating specificity of induction. Thus we
have identified novel components of a complex, coordinated genetic
program that is induced in striatal cells in response to various
dopaminergic manipulations.
Key words:
dopamine; striatum; CREB; differential display PCR; immediate-early genes; neuronal plasticity; addiction
Copyright © 1998 Society for Neuroscience 0270-6474/98/18145301-10$05.00/0
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