EFFECTS OF L-DOPA ON EXTRACELLULAR DOPAMINE IN STRIATUM OF NORMAL AND 6-HYDROXYDOPAMINE-TREATED RATS

In vivo microdialysis was used to examine the effect of l-3,4-dihydroxyphenylalanine (l-DOPA) administration upon dopamine (DA) in extracellular fluid both in intact striatum and in striatum of rats treated with the catecholaminergic neurotoxin 6-hydroxydopamine (6-HDA). Basal extracellular levels of DA were not significantly altered by 6-HDA unless the DA content of striatal tissue was reduced to less than 20% of control. Peripheral aromatic amino acid decarboxylase (AADC) inhibition (RO4-4602, 50 mg/kg i.p.) followed by l-DOPA treatment (100 mg/kg i.p.) elevated extracellular DA in striatum of control rats from 37 ± 5 to 68 ± 11 pg/sample (n = 7); values corrected for recovery of the dialysis probe). In animals with severe bilateral depletions of DA in striatal tissue (mean depletion 87%; n = 6), l-DOPA increased extracellular DA in striatum from 8 ± 3 to 266 ± 60 pg/sample. In animals with large unilateral depletions of DA in striatal tissue (mean depletion 96%; n = 6), the increase in extracellular DA in striatum after l-DOPA was greater on the lesion side (from 7 ± 4 to 245 ± 67 pg/sample) than on the intact side (from 28 ± 11 to 61 ± 8 pg/sample). Animals with unilateral DA depletions showed contralateral circling behavior afterl-DOPA. Increases in extracellular DA approaching the magnitude of those occuring in DA-depleted striata were observed when intact animals were treated with nomifensine (5 mg/kg i.p.; n = 5), an inhibitor of high-affinity DA uptake, in addition to l-DOPA. © 1990.