Impact of L-DOPA on striatal acetylcholine release: Effects of 6- hydroxydopamine

D. Jackson, E. D. Abercrombie, M. J. Zigmond

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16 Scopus citations

Abstract

We investigated the effects of the dopamine (DA) precursor L- dihydroxyphenylalanine (L-DOPA) on electrically evoked acetylcholine (ACh) overflow from rat striatal slices. Some animals were pretreated 1 to 2 months earlier with 6-hydroxydopamine, (6-OHDA), a catecholamine neurotoxin, so as to selectively destroy DA terminals (98.6% striatal DA depletion). Although the addition of L-DOPA (10 μM) produced a 37% inhibition of ACh overflow in slices from lesioned rats, it failed to affect ACh overflow in slices from intact animals. In contrast, ACh overflow from intact slices exposed to L- DOPA and to the DA uptake inhibitor nomifensine (1 μM) was 22% greater than in the presence of nomifensine without L-DOPA. ACh overflow from slices prepared from lesioned rats was 45% greater with both drugs than in the presence of nomifensine by itself. Superfusion with the aromatic L-amino acid decarboxylase (AADC) inhibitor NSD-1055 (250 μM) abolished the inhibitory effects of L-DOPA, as did L-sulpiride (1 μM), an inhibitor of DA receptors of the D2 subtype. These results suggest that inhibition of ACh overflow by L-DOPA is mediated by DA formed from exogenous L-DOPA which then acts on D2 receptors. They further indicate that the net impact of the loss of nigrostriatal terminals is an increased dopaminergic inhibition of striatal cholinergic interneurons in response to exogenous L-DOPA. This appears to result in large part from a lesion-induced reduction in high-affinity reuptake of DA formed from exogenous L-DOPA.

Original languageEnglish (US)
Pages (from-to)912-918
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number2
StatePublished - 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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