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 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 D2 receptor binding in the affected areas of the striatum was 28.8 +/- 1.0% for 4.74 micrograms dopamine/h infusion rate, 35.0 +/- 1.6% for 9.48 micrograms dopamine/h infusion rate and 33.3 +/- 5.0% for 14.22 micrograms 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.
Woiciechowsky
C
C
Department of Neurosurgery, Humboldt-University, Medical School (Charité), Berlin, Germany.
Guilarte
T R
TR
May
C H
CH
Vesper
J
J
Wagner
H N
HN
Vogel
S
S
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001345:Autoradiography; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D007839:Functional Laterality; D015918:Infusion Pumps, Implantable; D008297:Male; D016627:Oxidopamine; D011869:Radioligand Assay; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects; D012399:Rotation; D013134:Spiperone / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D013134:Spiperone; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine