Comparative studies of the neurotoxicity of MPTP in rats of different ages.
The present study investigated the neurotoxic effects of repeated MPTP injections on monoamine neurotransmitters and locomotor activity in rats of different ages. We also examined the mortality of MPTP-treated rats at different ages. Male Sprague-Dawley rats were used in all experiments. In the first experiment, we examined the mortality of rats (11-12 month old) subject to different doses of MPTP. In the second experiment, rats of 2-3 months old were randomly divided into five groups. Group 1 served as the control; Groups 2,3,4 and 5 received daily MPTP injections (30 mg/kg, ip) for a continuation of 7 days. Biochemical and behavioral assays were conducted at 1,7,14 and 28 days after withdrawal of MPTP, respectively. In the third and fourth experiments, the same experimental design was adopted except that rats of 5-6 months old and rats of 11-12 months old were used, respectively. Besides, the doses of MPTP used were 22.5 mg/kg and 12.5 mg/kg, respectively. Immunohistochemical experiments were always conducted 7 days after withdrawal of MPTP. Results indicated that, in young rats, repeated MPTP injections did not significantly decrease DA, and 5HT levels as well as TH and DBH immunoreactivities although it impaired locomotor activity. The same treatment significantly depleted DA, NE and 5HT levels in the middle-aged rats. It also decreased the density of TH and DBH immunoreactivities and altered the morphology of DA and NE neurons. Meanwhile, it impaired locomotor activity. In old rats, MPTP injections produced effects similar to those observed in the middle-age rats except that the hippocampal serotonergic system was also affected. However, all these effects recovered 28 days after withdrawal of MPTP injection. Finally, the dose of MPTP required to exert similar extent of neurotoxicity decreased as the age of rats increased, and the dose required to result in mortality markedly decreased in old rats. These results together suggest that MPTP does exert a toxicity on DA, NE and 5HT neurons and impair motor activity in rats. These effects are age-dependent while the irreversibility of MPTP's toxicity in rats requires further investigation.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
E H
EH
Lee
S P
SP
Liu
K T
KT
Lu
W R
WR
Lin
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000201:enzymology / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D007150:Immunohistochemistry; D020267:MPTP Poisoning; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; D012701:Serotonin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D009638:Norepinephrine