Document Detail

Dopamine D1 receptor modulation of glutamate receptor messenger RNA levels in the neocortex and neostriatum of unilaterally 6-hydroxydopamine-lesioned rats.
MedLine Citation:
PMID:  10199613     Owner:  NLM     Status:  MEDLINE    
The effect of treatment with the D1 dopamine receptor agonist SKF 38393 on the expression of metabotropic glutamate receptor 1, 3, 4 and 5 receptor subtypes and of the glutamate N-methyl-D-aspartate ionotropic receptor subunits NRI, NR2A and NR2B was analysed using in situ hybridization. We studied the neocortex and neostriatum of normal rats and of rats unilaterally treated with 6-hydroxydopamine, a neurotoxin that, after intracerebral injection into the ventral tegmental area, causes selective degeneration of the ascending dopamine pathway. In the 6-hydroxydopamine-lesioned rats, metabotropic glutamate receptor subtype 3 messenger RNA levels were ipsilaterally increased in the neocortex and neostriatum, while the levels of metabotropic glutamate receptor subtype 4 messenger RNA were bilaterally increased in both regions. When administered to the 6-hydroxydopamine-lesioned rats, the D1 receptor agonist SKF 38393 (3 x 20 mg/kg, s.c.) produced a bilateral decrease in the expression of the metabotropic glutamate receptor subtype 1 and 5 receptor messenger RNA levels in the neocortex and neostriatum. In the neostriatum, SKF 38393 attenuated the ipsilateral increase in the expression of striatal metabotropic glutamate receptor subtype 3 messenger RNA produced by the 6-hydroxydopamine lesion. Furthermore, SKF 38393 produced a bilateral decrease in the levels of NRI receptor subunit messenger RNA and, in contrast, an increase in the striatal NR2B messenger RNA levels. All of these effects were abolished by the D1 receptor antagonist SCH 23360. These results indicate a differential D1 receptor-mediated modulation of the expression of some glutamate receptor subtypes in the neostriatum and neocortex, in agreement with the idea of a functional coupling between dopamine and excitatory amino acid systems in both regions. Thus, pharmacological targeting of excitatory amino acid systems could provide alternative or complementary treatment strategies for diseases involving dopaminergic systems in the striatum (e.g., Parkinson's disease) and cortex (e.g., schizophrenia).
R Rodríguez-Puertas; M Herrera-Marschitz; J Koistinaho; T Hökfelt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience     Volume:  89     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-07-07     Completed Date:  1999-07-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  781-97     Citation Subset:  IM    
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
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MeSH Terms
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology*
Corpus Striatum / drug effects*,  metabolism
Dopamine / physiology*
Dopamine Agonists / pharmacology*
Drug Design
Gene Expression Regulation / drug effects*
Glutamic Acid / physiology
In Situ Hybridization
Motor Activity / drug effects,  physiology
Neocortex / drug effects*,  metabolism
Nerve Tissue Proteins / biosynthesis*,  genetics
Neurotoxins / toxicity*
Oxidopamine / toxicity*
Parkinson Disease / drug therapy
RNA, Messenger / biosynthesis*,  genetics
Rats, Sprague-Dawley
Receptors, Dopamine D1 / agonists,  drug effects,  physiology*
Receptors, Metabotropic Glutamate / biosynthesis*,  genetics
Schizophrenia / drug therapy
Stereotyped Behavior / drug effects
Sympatholytics / toxicity
Tegmentum Mesencephali / drug effects,  metabolism
Reg. No./Substance:
0/Dopamine Agonists; 0/Nerve Tissue Proteins; 0/Neurotoxins; 0/RNA, Messenger; 0/Receptors, Dopamine D1; 0/Receptors, Metabotropic Glutamate; 0/Sympatholytics; 1199-18-4/Oxidopamine; 56-86-0/Glutamic Acid; 67287-49-4/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine

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