Effects of iptakalim on extracellular glutamate and dopamine levels in the striatum of unilateral 6-hydroxydopamine-lesioned rats: a microdialysis study.
In a previous study, we demonstrated that iptakalim (Ipt) significantly ameliorated hypolocomotion and catalepsy induced by haloperidol and rotenone in rats. In order to further understand the mechanism(s), using a rat model of Parkinson's disease (PD) established by unilateral 6-hydroxydopamine (6-OHDA) administration to the substantia nigra pars compacta (SNpc) and reverse microdialysis techniques with high performance liquid chromatography (HPLC), we investigated the effects of Ipt on extracellular levels of glutamate, dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in the striatum of conscious and freely moving rats. The results indicated that unilateral 6-OHDA-lesioned rats have a significantly higher level of extracellular glutamate and a lower level of extracellular DOPAC in the lesioned-side of the striatum, and a lower level of extracellular DA in both sides of the striatum compared to the striatum of control rats. Ipt reduced extracellular glutamate levels in both sides of striatum of the lesioned and control rats in a concentration-dependent manner. Ipt, at lower concentrations (0.01, 0.1, 1 microM), enhanced extracellular DA levels in the lesioned-side striatum of the unilateral 6-OHDA-lesioned rats, while causing no significant changes in the intact side striatum, and even a significant decline in striatum of control rats at higher concentrations of Ipt (10, 100 microM). In addition, Ipt also caused a significant decline in the extracellular DOPAC levels in the lesioned-side striatum of unilateral 6-OHDA-lesioned rats. These data suggest that the major mechanism underlying the ameliorative effects of Ipt on the behavior in 6-OHDA-lesioned rats is the alteration of levels of extracellular neurotransmitters, such as glutamate and DA in the striatum of unilateral 6-OHDA-lesioned rats.
Yang
Jian
J
Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing 210029, PR China.
Hu
Li-fang
LF
Liu
Xing
X
Zhou
Fang
F
Ding
Jian-hua
JH
Hu
Gang
G
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D016627:Oxidopamine / Q000633:toxicity; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines; D015102:3,4-Dihydroxyphenylacetic Acid; D018698:Glutamic Acid; D016627:Oxidopamine; D004298:Dopamine