Elevation of dopamine D2 but not D1 receptors in adult rat neostriatum after neonatal 6-hydroxydopamine denervation.
Monoamine levels and the binding properties of [3H]SCH23390, a D1-specific ligand, and [3H]raclopride, a D2-specific ligand, were measured in the rostal and caudal neostriatum to investigate the fate of dopamine receptors following bilateral cerebroventricular injection of 6-hydroxydopamine in 3-day-old rats. After survival times of 15, 30 or 90 days, measurement of monoamine levels and of [3H]SCH23390 binding were also obtained from the cerebral cortex. At all three survival times, dopamine content was reduced by more than 90% of control values in both the rostral and caudal neostriatum; in cerebral cortex, the dopamine depletion was less profound (80%) and noticeable only after 1 and 3 months. In the rostral but not the caudal neostriatum, serotonin and 5-hydroxyindoleacetic acid concentrations were markedly increased at 1 and 3 months; cortical serotonin also was augmented at 3 months. There were no changes in neostriatal [3H]SCH23390 binding at any of the survival times, but a transient elevation occurred in the cortex at 1 month. In the rostral but not the caudal neostriatum, [3H]raclopride binding showed a slight elevation at 1 month and a further, highly significant increase at 3 months. As measured in individual rats, this increase in [3H]raclopride binding was linearly correlated with the increase in serotonin turnover (ratio of 5-hydroxyindoleacetic acid/serotonin). Such an up-regulation of D2 receptors, restricted to the rostral neostriatum which was also the site of a serotonin hyperinnervation, was probably indicative of a serotonin control on the expression of D2 receptors after dopamine denervation.
Dewar
K M
KM
Département de Physiologie, Université de Montréal, Qué., Canada.
Soghomonian
J J
JJ
Bruno
J P
JP
Descarries
L
L
Reader
T A
TA
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D015306:Biogenic Monoamines / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D016627:Oxidopamine; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D015306:Biogenic Monoamines; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016627:Oxidopamine