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
✍ Scribed by Shaharyar M. Khan; Trisha S. Smith; James P. Bennett Jr.
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 383 KB
- Volume
- 55
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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 35 Sguanosine-5Ј (␥-thio) triphosphate ( 35 S-GTP-␥-S) binding to striatal sections. Reserpine treatment increased both basal and maximal striatal DA-stimulated 35 S-GTP-␥-S binding. The augmented IEG responses to single L-DOPA treatments involved dependency on both D1 and D2 receptors and acutely to N-methyl-Daspartate (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.