 |
 Previous Article | Next Article 
The Journal of Neuroscience, June 15, 2002, 22(12):5042-5054
D1 Dopamine Receptor Supersensitivity in the
Dopamine-Depleted Striatum Results from a Switch in the
Regulation of ERK1/2/MAP Kinase
Charles R.
Gerfen,
Shigehiro
Miyachi,
Ronald
Paletzki, and
Pierre
Brown
Laboratory of Systems Neuroscience, National Institute of Mental
Health, Bethesda, Maryland 20892-4075
Dopamine effects in the striatum are mediated principally through
the D1 and D2 dopamine receptor subtypes, which are segregated to the
direct and indirect striatal projection neurons. After degeneration of
the nigrostriatal dopamine system, direct pathway neurons display a
supersensitive response to D1 dopamine receptor agonists, which is
demonstrated by the induction of immediate early genes (IEGs), such as
c-fos. Here we show, using analysis of
receptor-mediated signal transduction, including protein
phosphorylation and induction of IEGs, that D1 dopamine receptor
supersensitivity is attributable to a switch to
ERK1/2/MAP kinase (extracellular signal-regulated
kinase/mitogen-activated protein kinase) in direct pathway neurons.
Normally, in the dopamine-intact striatum, activation of ERK1/2/MAP
kinase is shown to be restricted to indirect and not direct pathway
neurons in response to stimulation of corticostriatal afferents.
Moreover, in the dopamine-intact striatum, treatment with full D1
dopamine receptor agonists or stimulation of nigrostriatal dopaminergic
afferents, both of which result in the induction of IEGs in direct
striatal projection neurons, does not activate ERK1/2/MAP kinase.
However, after degeneration of the nigrostriatal dopaminergic pathway,
ERK1/2/MAP kinase is activated in direct pathway neurons in response to
D1 dopamine receptor agonists either alone or when combined with
stimulation of corticostriatal afferents. Inhibitors of MEK (MAP kinase
kinase), which is responsible for phosphorylation of ERK1/2/MAP kinase,
blocks D1 dopamine receptor agonist activation of ERK1/2/MAP kinase in
the dopamine-depleted striatum, as well as the supersensitive induction
of IEGs. These results demonstrate that dopamine input to the striatum
maintains distinct forms of protein kinase-mediated gene regulation in
the direct and indirect striatal projection neurons.
Key words:
dopamine; striatum; Parkinson's disease; gene
regulation; signal transduction; MAP kinase; protein kinase
Copyright © 2002 Society for Neuroscience 0270-6474/02/22125042-13$05.00/0
This article has been cited by other articles:
|
|
|
|
 
E. Santini, M. Heiman, P. Greengard, E. Valjent, and G. Fisone
Inhibition of mTOR Signaling in Parkinson's Disease Prevents L-DOPA-Induced Dyskinesia
Sci. Signal.,
July 21, 2009;
2(80):
ra36 - ra36.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Rylander, A. Recchia, F. Mela, A. Dekundy, W. Danysz, and M. A. Cenci
Pharmacological Modulation of Glutamate Transmission in a Rat Model of L-DOPA-Induced Dyskinesia: Effects on Motor Behavior and Striatal Nuclear Signaling
J. Pharmacol. Exp. Ther.,
July 1, 2009;
330(1):
227 - 235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Pisani and J. Shen
Levodopa-induced dyskinesia and striatal signaling pathways
PNAS,
March 3, 2009;
106(9):
2973 - 2974.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Crittenden, I. Cantuti-Castelvetri, E. Saka, C. E. Keller-McGandy, L. F. Hernandez, L. R. Kett, A. B. Young, D. G. Standaert, and A. M. Graybiel
Dysregulation of CalDAG-GEFI and CalDAG-GEFII predicts the severity of motor side-effects induced by anti-parkinsonian therapy
PNAS,
February 24, 2009;
106(8):
2892 - 2896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Kheirbek, J. A. Beeler, Y. Ishikawa, and X. Zhuang
A cAMP Pathway Underlying Reward Prediction in Associative Learning
J. Neurosci.,
October 29, 2008;
28(44):
11401 - 11408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. B. Dupre
A Potential Neuroanatomical Dissociation of DARPP-32 in Striatal ERK Signaling
J. Neurosci.,
October 22, 2008;
28(43):
10783 - 10785.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Gerfen, R. Paletzki, and P. Worley
Differences between Dorsal and Ventral Striatum in Drd1a Dopamine Receptor Coupling of Dopamine- and cAMP-Regulated Phosphoprotein-32 to Activation of Extracellular Signal-Regulated Kinase
J. Neurosci.,
July 9, 2008;
28(28):
7113 - 7120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Bertran-Gonzalez, C. Bosch, M. Maroteaux, M. Matamales, D. Herve, E. Valjent, and J.-A. Girault
Opposing Patterns of Signaling Activation in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons in Response to Cocaine and Haloperidol
J. Neurosci.,
May 28, 2008;
28(22):
5671 - 5685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Schuster, A. Nadjar, J. T. Guo, Q. Li, C. Ittrich, B. Hengerer, and E. Bezard
The 3-Hydroxy-3-Methylglutaryl-CoA Reductase Inhibitor Lovastatin Reduces Severity of L-DOPA-Induced Abnormal Involuntary Movements in Experimental Parkinson's Disease
J. Neurosci.,
April 23, 2008;
28(17):
4311 - 4316.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Millan, P. Svenningsson, C. R. Ashby Jr., M. Hill, M. Egeland, A. Dekeyne, M. Brocco, B. Di Cara, F. Lejeune, N. Thomasson, et al.
S33138 [N-[4-[2-[(3aS,9bR)-8-Cyano-1,3a,4,9b-tetrahydro[1]-benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenylacetamide], a Preferential Dopamine D3 versus D2 Receptor Antagonist and Potential Antipsychotic Agent. II. A Neurochemical, Electrophysiological and Behavioral Characterization in Vivo
J. Pharmacol. Exp. Ther.,
February 1, 2008;
324(2):
600 - 611.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Rommelfanger, G. L. Edwards, K. G. Freeman, L. C. Liles, G. W. Miller, and D. Weinshenker
Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice
PNAS,
August 21, 2007;
104(34):
13804 - 13809.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Santini, E. Valjent, A. Usiello, M. Carta, A. Borgkvist, J.-A. Girault, D. Herve, P. Greengard, and G. Fisone
Critical Involvement of cAMP/DARPP-32 and Extracellular Signal-Regulated Protein Kinase Signaling in L-DOPA-Induced Dyskinesia
J. Neurosci.,
June 27, 2007;
27(26):
6995 - 7005.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Quiroz, C. Gomes, A. C. Pak, J. A. Ribeiro, S. R. Goldberg, B. T. Hope, and S. Ferre
Blockade of Adenosine A2A Receptors Prevents Protein Phosphorylation in the Striatum Induced by Cortical Stimulation.
J. Neurosci.,
October 18, 2006;
26(42):
10808 - 10812.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Li, H. Guo, X. Luo, J. Sheng, S. Yang, Y. Yin, J. Zhou, and J. Zhou
Apomorphine-induced activation of dopamine receptors modulates FGF-2 expression in astrocytic cultures and promotes survival of dopaminergic neurons
FASEB J,
June 1, 2006;
20(8):
1263 - 1265.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. K. Tofaris, P. Garcia Reitbock, T. Humby, S. L. Lambourne, M. O'Connell, B. Ghetti, H. Gossage, P. C. Emson, L. S. Wilkinson, M. Goedert, et al.
Pathological Changes in Dopaminergic Nerve Cells of the Substantia Nigra and Olfactory Bulb in Mice Transgenic for Truncated Human {alpha}-Synuclein(1-120): Implications for Lewy Body Disorders
J. Neurosci.,
April 12, 2006;
26(15):
3942 - 3950.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Fiorentini, M. C. Rizzetti, C. Busi, S. Bontempi, G. Collo, P. Spano, and C. Missale
Loss of Synaptic D1 Dopamine/N-Methyl-D-aspartate Glutamate Receptor Complexes in L-DOPA-Induced Dyskinesia in the Rat
Mol. Pharmacol.,
March 1, 2006;
69(3):
805 - 812.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Valjent, V. Pascoli, P. Svenningsson, S. Paul, H. Enslen, J.-C. Corvol, A. Stipanovich, J. Caboche, P. J. Lombroso, A. C. Nairn, et al.
From The Cover: Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum
PNAS,
January 11, 2005;
102(2):
491 - 496.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chen, M. Rusnak, R. R. Luedtke, and A. Sidhu
D1 Dopamine Receptor Mediates Dopamine-induced Cytotoxicity via the ERK Signal Cascade
J. Biol. Chem.,
September 17, 2004;
279(38):
39317 - 39330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. T. Papadeas, B. L. Blake, D. J. Knapp, and G. R. Breese
Sustained Extracellular Signal-Regulated Kinase 1/2 Phosphorylation in Neonate 6-Hydroxydopamine-Lesioned Rats after Repeated D1-Dopamine Receptor Agonist Administration: Implications for NMDA Receptor Involvement
J. Neurosci.,
June 30, 2004;
24(26):
5863 - 5876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Gerfen
D1 Dopamine Receptor Supersensitivity in the Dopamine-Depleted Striatum Animal Model of Parkinson's Disease
Neuroscientist,
December 1, 2003;
9(6):
455 - 462.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. A. Moron, I. Zakharova, J. V. Ferrer, G. A. Merrill, B. Hope, E. M. Lafer, Z. C. Lin, J. B. Wang, J. A. Javitch, A. Galli, et al.
Mitogen-Activated Protein Kinase Regulates Dopamine Transporter Surface Expression and Dopamine Transport Capacity
J. Neurosci.,
September 17, 2003;
23(24):
8480 - 8488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Iwamoto, S. Okumura, K. Iwatsubo, J.-I. Kawabe, K. Ohtsu, I. Sakai, Y. Hashimoto, A. Izumitani, K. Sango, K. Ajiki, et al.
Motor Dysfunction in Type 5 Adenylyl Cyclase-null Mice
J. Biol. Chem.,
May 2, 2003;
278(19):
16936 - 16940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Lindgren, A. Usiello, M. Goiny, J. Haycock, E. Erbs, P. Greengard, T. Hokfelt, E. Borrelli, and G. Fisone
Distinct roles of dopamine D2L and D2S receptor isoforms in the regulation of protein phosphorylation at presynaptic and postsynaptic sites
PNAS,
April 1, 2003;
100(7):
4305 - 4309.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Nishi, F. Liu, S. Matsuyama, M. Hamada, H. Higashi, A. C. Nairn, and P. Greengard
Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling
PNAS,
February 4, 2003;
100(3):
1322 - 1327.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Baufreton, M. Garret, A. Rivera, A. de la Calle, F. Gonon, B. Dufy, B. Bioulac, and A. Taupignon
D5 (Not D1) Dopamine Receptors Potentiate Burst-Firing in Neurons of the Subthalamic Nucleus by Modulating an L-Type Calcium Conductance
J. Neurosci.,
February 1, 2003;
23(3):
816 - 825.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
