Intrastriatal Dopamine Infusion Reverses Compensatory Increases in D2-Dopamine Receptors in the 6-OHDA Lesioned Rat

Direct infusion of dopamine into the corpus striatum has been proposed as a potential approach for the treatment of Parkinson's disease. The present study examined the effect of intrastriatal dopamine infusion on D2-dopamine receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat brain. The co...

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Bibliographic Details
Published in:Neurodegeneration (London, England) England), 1995-06, Vol.4 (2), p.161-169
Main Authors: Woiciechowsky, Christian, Guilarte, Tomás R., May, Christiane H., Vesper, Jan, Wagner Jr, Henry N., Vogel, Siegfried
Format: Article
Language:English
Subjects:
6-OHDA
Animals
Apomorphine - pharmacology
Autoradiography
corpus striatum
Corpus Striatum - drug effects
Corpus Striatum - metabolism
D2-dopamine receptors
dopamine
Dopamine - pharmacology
Functional Laterality
Infusion Pumps, Implantable
Male
Oxidopamine
Parkinson's disease
Radioligand Assay
rat
Rats
Receptors, Dopamine D2 - drug effects
Receptors, GABA-A - drug effects
Rotation
Spiperone - metabolism
Substantia Nigra - drug effects
Substantia Nigra - metabolism
Up-Regulation - drug effects
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Summary:Direct infusion of dopamine into the corpus striatum has been proposed as a potential approach for the treatment of Parkinson's disease. The present study examined the effect of intrastriatal dopamine infusion on D2-dopamine receptors in the 6-hydroxydopamine (6-OHDA) lesioned rat brain. The completeness of the 6-OHDA-induced nigrostriatal injury was confirmed using [3H]-mazindol autoradiography and apomorphine-induced behaviour. Intrastriatal infusion of three different dopamine doses significantly reduced the apomorphine-induced behaviour. [3H]-spiperone autoradiography performed one day after the termination of dopamine infusion into the striatum revealed a dramatic reduction of D2-dopamine receptor binding. The mean ± SEM percent reduction of D2receptor binding in the affected areas of the striatum was 28.8±1.0% for 4.74 μg dopamine/h infusion rate, 35.0 ± 1.6% for 9.48 μg dopamine/h infusion rate and 33.3 ± 5.0% for 14.22 μg dopamine/h infusion rate when compared to the unlesioned side. Infusion of vehicle alone did not have any effect. The present results support the concept that intrastriatal dopamine infusion may be a useful therapeutic approach for the treatment of Parkinson's disease.
ISSN:1055-8330
1522-9661
DOI:10.1006/neur.1995.0020