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 after L-DOPA. Increases in extracellular DA approaching the magnitude of those occurring 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.
Abercrombie
E D
ED
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Bonatz
A E
AE
Zigmond
M J
MJ
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects*; D006892:Hydroxydopamines / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009627:Nomifensine / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D006892:Hydroxydopamines; D009627:Nomifensine; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine