D(1) AND D(2) DOPAMINE-RECEPTORS DO NOT UP-REGULATE IN RESPONSE TO NEONATAL INTRASTRIATAL 6-HYDROXYDOPAMINE LESIONS

The extent of dopamine (DA) depletion appears to exert important influ ences on the plasticity of the DA system following lesions made in adu lthood. The aim of this study was to determine if the extent of DA dep letion has long-term effects on DA receptor regulation after early neo natal lesions. Early intrastriatal injections of 6-hydroxydopamine (6- OHDA) caused a dose-dependent loss of high-affinity DA uptake sites an d mu-opioid receptor patches evident in adulthood. DA receptors did no t up-regulate in response to any degree of neonatal DA depletion. A pa tchy loss of D1 binding was evident following the neonatal lesions, al though the loss was somewhat more severe and uniform with the highest dose of 6-OHDA (20 mug per striatum). There was also a slight decrease in D2 binding which was not dose-dependent. These results suggest tha t 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.