Chronic high dose L-dopa treatment does not alter the levels of dopamine D-1, D-2 or D-3 receptor in the striatum of normal monkeys: an autoradiographic study.
To assess the role of dopamine receptors in the genesis of dyskinesia, we have used quantitative autoradiography to determine the effect of chronic L-dopa administration on dopamine D-1 (using [3H]SCH 23390), D-2 (using [3H]spiperone) and D-3 (using [3H]7-OH-DPAT) receptor binding levels in the striatum of dyskinetic or non-dyskinetic monkeys. Total and subregional striatal analysis showed no difference in D-1, D-2 or D-3 receptor binding in the caudate and putamen between monkeys receiving high dose L-dopa treatment with marked dyskinesia and those without dyskinesia compared to untreated animals. It thus appears unlikely that changes in dopamine receptor expression are a primary cause of L-dopa induced dyskinesia. Rather, a functional dissociation of D-2 receptor coupling to co-expressed enkephalin/adenosine-2a receptor activity in the striato-GPe indirect pathway may be more important in the development or expression of L-dopa-induced involuntary movements.
Zeng
B Y
BY
Neurodegenerative Disease Research Centre, Guy's, King's and St Thomas' School of Biomedical Sciences, King's College, London, United Kingdom.
Pearce
R K
RK
MacKenzie
G M
GM
Jenner
P
P
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D007980:Levodopa / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D043705:Receptor, Adenosine A2A; D011954:Receptors, Dopamine; D018047:Receptors, Purinergic P1; D007980:Levodopa