L-DOPA regulates glutamate decarboxylases mRNA levels in MPTP-treated monkeys.
The effect of dopaminergic denervation, alone or followed by chronic intermittent L-DOPA administration, on the levels of mRNAs encoding for the two isoforms of the GABA-synthesizing enzyme, glutamate decarboxylase (GAD65 and GAD67), were measured by in-situ hybridization in the caudate and putamen of macaque monkeys. When compared to control monkeys, the level of GAD67 mRNA was increased in the putamen and caudate of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. On the other hand, GAD65 mRNA labeling in MPTP-treated monkeys was not significantly different from the controls. In MPTP-treated monkeys that received L-DOPA, a significant increase in both GAD67 and GAD65 mRNA levels was measured in the putamen when compared to control or MPTP-treated monkeys. The results suggest that the dyskinetic effect of L-DOPA is paralleled by an increased GABAergic activity in the striatum.
Soghomonian
J J
JJ
Centre de Recherche en Neurobiologie, Université Laval, Hôpital de l'Enfant-Jésus, Quebec, Canada.
Pedneault
S
S
Blanchet
P J
PJ
Goulet
M
M
Di Paolo
T
T
Bédard
P J
PJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000187:drug effects* / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology*; D008251:Macaca; D011699:Putamen / Q000187:drug effects; D014965:X-Rays
D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005968:Glutamate Decarboxylase