D1 and D2 dopamine receptors do not up-regulate in response to neonatal intrastriatal 6-hydroxydopamine lesions.
The extent of dopamine (DA) depletion appears to exert important influences on the plasticity of the DA system following lesions made in adulthood. The aim of this study was to determine if the extent of DA depletion has long-term effects on DA receptor regulation after early neonatal lesions. Early intrastriatal injections of 6-hydroxydopamine (6-OHDA) caused a dose-dependent loss of high-affinity DA uptake sites and mu-opioid receptor patches evident in adulthood. DA receptors did not up-regulate in response to any degree of neonatal DA depletion. A patchy loss of D1 binding was evident following the neonatal lesions, although the loss was somewhat more severe and uniform with the highest dose of 6-OHDA (20 micrograms per striatum). There was also a slight decrease in D2 binding which was not dose-dependent. These results suggest that the consequences of early neonatal DA lesions are not dependent upon the degree of DA depletion, as the effects on DA receptor expression were similar regardless of the extent of the lesions.
Neal-Beliveau
B S
BS
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104.
Joyce
J N
JN
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001345:Autoradiography; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D005260:Female; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D016627:Oxidopamine; D003891:Desipramine