Effects of l-DOPA on extracellular dopamine in striatum of normal and 6-hydroxydopamine-treated rats

Abstract

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 decar☐ylase (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 from37 ± 5to68 ± 11pg/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 from8 ± 3to266 ± 60pg/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(from7 ± 4to245 ± 67pg/sample) than on the intact side(from28 ± 11to61 ± 8pg/sample). Animals with unilateral DA depletions showed contralateral circling behavior after l-DOPA. Increases in extracellular DA approaching the magnitude of those occuring in DA-depleted striata were observed when intact animals were treated with nomifensine(5mg/kg i.p.; n = 5), an inhibitor of high-affinity DA uptake, in addition to l-DOPA.