Reuptake of L-DOPA-derived extracellular DA in the striatum of a rodent model of Parkinson's disease via norepinephrine transporter.
To determine the role of norepinephrine transporter in reuptake of L-DOPA-derived extracellular DA in the DA-denervated Parkinsonian striatum, we examined extracellular DA levels in the striatum of 6-hydroxyDA-lesioned rats that received L-DOPA (50 mg/kg with 12.5 mg/kg of benserazide) and L-DOPA plus desipramine (25 mg/kg), a selective norepinephrine reuptake inhibitor, using in vivo microdialysis. The pretreatment with desipramine increased levels of extracellular DA derived from administrated L-DOPA in the DA-denervated striatum. This study provides evidence that L-DOPA-derived DA is taken up by the norepinephrine transporter, instead of the dopamine transporter, in the striatum with dopaminergic denervation. This result suggests that the norepinephrine transporter could be a promising target in the treatment for Parkinson's disease.
Arai
Akira
A
Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Tomiyama
Masahiko
M
Kannari
Kazuya
K
Kimura
Tamaki
T
Suzuki
Chieko
C
Watanabe
Mitsunori
M
Kawarabayashi
Takeshi
T
Shen
Huo
H
Shoji
Mikio
M
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D003714:Denervation; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D050484:Norepinephrine Plasma Membrane Transport Proteins; D007980:Levodopa; D016627:Oxidopamine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine