Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 5,7-dihydroxytryptamine on the locomotor activity and...

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.