Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 5,7-dihydroxytryptamine on the locomotor activity and striatal amines in C57BL/6 mice.
The present study examined the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 5,7-dihydroxytryptamine (5,7-DHT) on striatal levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites homovanillic acid (HVA) and 5-hydroxyindole-3-acetic acid (5-HIAA), respectively, as well as their influence on locomotor activity in conscious C57BL/6 mice. High doses (s.c., 35-45 mg/kg per day for 10 days) of MPTP resulted in a significant (P < 0.05) increase in locomotor activity and a marked decrease of striatal DA levels. Concomitantly, the ratios of HVA to DA and 5-HIAA to 5-HT increased significantly, the latter reflecting increased 5-HIAA levels. In contrast, i.c.v. administration of the serotonergic neurotoxin 5,7-DHT, either alone or following high doses (40 mg/kg per day for 10 days) of MPTP, decreased locomotor activity. Furthermore, striatal levels of 5-HT and 5-HIAA as well as the 5-HIAA/5-HT ratio decreased significantly. Thus, the increased locomotor activity induced by chronic high doses of MPTP might be due to increased striatal 5-HT levels which appear to compensate for the loss of DA. Furthermore, the locomotor hypoactivity induced by 5,7-DHT may be secondary to the striatal 5-HT deficiency.
Chia
L G
LG
Section of Neurology, Taichung Veterans General Hospital, Taiwan, ROC.
Ni
D R
DR
Cheng
L J
LJ
Kuo
J S
JS
Cheng
F C
FC
Dryhurst
G
G
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL
D001679:Biogenic Amines; D015116:5,7-Dihydroxytryptamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine