IMPACT OF L-DOPA ON STRIATAL ACETYLCHOLINE-RELEASE - EFFECTS OF 6-HYDROXYDOPAMINE

We investigated the effects of the dopamine (DA) precursor L-dihydroxy phenylalanine (L-DOPA) on electrically evoked acetylcholine (ACh) over flow from rat striatal slices. Some animals were pretreated 1 to 2 mon ths earlier with 6-hydroxydopamine, (6-OHDA), a catecholamine neurotox in, so as to selectively destroy DA terminals (98.6% striatal DA deple tion). Although the addition of L-DOPA (10 muM) produced a 37% inhibit ion 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 no mifensine (1 muM) was 22% greater than in the presence of nomifensine without L-DOPA. ACh overflow from slices prepared from lesioned rats w as 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 muM) abolished the inhibitory effects of L-D OPA, as did L-sulpiride (1 muM), an inhibitor of DA receptors of the D 2 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 o f nigrostriatal terminals is an increased dopaminergic inhibition of s triatal cholinergic interneurons in response to exogenous L-DOPA. This appears to result in large part from a lesion-induced reduction in hi gh-affinity reuptake of DA formed from exogenous L-DOPA.