L-DOPA treatment of parkinsonian rats changes the expression of Src, Lyn and PKC kinases.
The dopamine (DA) precursor L-DOPA remains the most common treatment for Parkinson's disease (PD). However, long-term treatment with L-DOPA induces dyskinesia and motor disabilities in PD patients, indicating that this pharmacological agent is unable to fully compensate for the effects of DA denervation when used chronically. In this study, we examined the effect 6-hydroxydopamine (6-OHDA)-induced DA denervation of the striatum followed by either acute or chronic treatment with L-DOPA on gene expression of critical regulators of glutamate synaptic transmission. We found that administration of L-DOPA in rats with unilateral DA denervation resulted in a progressive increase of contraversive circling behavior and modulated the expression of Src, Lyn and PKC kinases. In particular, acute (3 days) and chronic (21 days) L-DOPA treatment were differentially able to rescue the effects of DA lesion, since only the acute treatment with L-DOPA corrected the decrease in Src, Lyn and PKC kinase expression induced by 6-OHDA lesion. Also, the reduced phosphorylation level of NR1 receptor subunit induced by 6-OHDA was only partially reversed by chronic L-DOPA treatment.
Napolitano
Maddalena
M
Dipartimento di Medicina Sperimentale e Patologia, Università La Sapienza, viale Regina Elena 324, 00161 Rome, Italy. maddalena.napolitano@uniroma1.it
Picconi
Barbara
B
Centonze
Diego
D
Bernardi
Giorgio
G
Calabresi
Paolo
P
Gulino
Alberto
A
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000201:enzymology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors; D019061:src-Family Kinases / Q000096:biosynthesis*
D000978:Antiparkinson Agents; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D016627:Oxidopamine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D011493:Protein Kinase C; D004298:Dopamine