Effects of single and multiple treatments with L‐dihydroxyphenylalanine (L‐DOPA) on dopamine receptor–G protein interactions and supersensitive immediate early gene responses in striata of rats after reserpine treatment or with unilateral nigrostriatal lesions

We studied effects of l ‐dihydroxyphenylalanine (L‐DOPA) treatment in rats following reserpine treatment or unilateral 6‐hydroxydopamine (6‐OHDA) injections into medial forebrain bundle. Quantitative in situ hybridization for mRNA's coding for the zinc finger immediate early gene (IEG) zif/268 or Jun family IEG jun b revealed that single L‐DOPA injections accentuated IEG expression 3‐ to 7‐fold in the dopamine (DA)‐depleted striatum. This increased IEG response did not derive from any alterations in DA receptor–G protein coupling, assayed by DA stimulation of ³⁵S‐guanosine‐5′ (γ‐thio) triphosphate (³⁵S‐GTP‐γ‐S) binding to striatal sections. Reserpine treatment increased both basal and maximal striatal DA‐stimulated ³⁵S‐GTP‐γ‐S binding. The augmented IEG responses to single L‐DOPA treatments involved dependency on both D1 and D2 receptors and acutely to N‐methyl‐d ‐aspartate (NMDA) channels. Repetitive L‐DOPA treatments yielded persistently elevated (zif/268) or additionally up‐regulated (jun b) IEG response in the denervated striatum and down‐regulated IEG responses in the control striatum. Degraded L‐DOPA responses and appearance of involuntary movements after chronic L‐DOPA use in advanced Parkinson's disease may derive from these IEG changes. J. Neurosci. Res. 55:71–79, 1999. © 1999 Wiley‐Liss, Inc.