Changes of Locomotor Activity and Biogenic Amines by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57BL/6 Mice

The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rodents was investigated by measuring the locomotor activity and the changes of brain biogenic amines in MPTP-treated C57BL/6 mice. The mice showed a typical curved spine posture 24 hours after MPTP treatment. Total locomotor activity was reduced and the ratios of stereotyped activity/total locomotor activity were increased 24 hours after MPTP treatment. However no significant changes were observed 7 days after MPTP treatment. MPTP-induced changes of biogenic amines were evident only in corpus striatum, not in frontal lobe, midbrain and hippocampus; the levels of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were reduced by 94%, 76.3% and 60.2% after 24 hours, and 81.9%, 61.3% and 26.1% after 6 days compared to control values respectively. The ratios of DOPAC/dopamine, HVA/dopamine and HVA/DOPAC were increased 24 hours and 7 day after MPTP treatment compared to control valuse in corpus striatum, but the degree of the 7 days was less than the 24 hours. The ratios of 5-HIAA/5-HT were incresed 24 hours and 7 days after MPTP treatment in corpus striatum, but there were no significant changes in the levels of 5-hydroxyindoleacetic acid (5-HIAA) and 5-hydroxtryptamine (5-HT). In conclusion, MPTP produced parkinsonism-like behavioral and biochemical changes in C57BL/ 6 mice.

Ischemia-induced Changes of Biogenic Amines in Rat Brain and the Effect of Nimodipine of Them

It has been reported that ischernia causes changes in the concentration and tumover of monoamine neurotransmitters in brain. For the mechanism of cellular death in brain ischernia it is suggested that accumulation of intracellular calcium during ischemia is one of the main causes. Present study was undertaken to investigate the influence of ischemia on the contents and tumover of the biogenic anines in rat brain and further to investigate the effects of nimodipine, a calcium channel blocker, and cromakalim, a potassium channel opener, on them. Brain ischemia was induced by partial ligation of bilateral common carotid artery. Nimodipine (36 ,ug/kg, I.p.) or cromakalim (0.5mg/kg, I.p.) was administered 20 minutes before ligation. Nimodipine was administered every 4 hours in 24-hour ischemic group. Rats were sacrificed by decapitation 3 or 24 hours after induction of ischemia and whole brains were excised. The brain was divided into follow ing regions; cerebral cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia nigra and cerebellum. The concentrations of biogenic amines and their metabolites were measured by high performance liquid chromatography-electrochemical detector (HPLC-ECD).