Chronic oral nicotine treatment protects against striatal degeneration in MPTP-treated primates.
The present studies were done to investigate the effect of long-term nicotine treatment against nigrostriatal damage in non-human primates. Monkeys were administered nicotine in drinking water for 6 months to provide chronic but intermittent delivery as with smoking. Plasma nicotine levels ranged from 10 to 15 ng/mL, which were within the range in cigarette smokers. Animals were then lesioned with low doses of the dopaminergic neurotoxin MPTP for several months while nicotine was continued. The results showed that levels of striatal tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter, dopamine and nicotinic receptors were greater in nicotine-treated MPTP-lesioned primates than in lesioned animals not receiving nicotine. Nicotine had no effect in unlesioned animals. Monoamine oxidase activity was similar in unlesioned and lesioned animals treated with or without nicotine, suggesting that nicotine did not exert its effects through changes in MPTP or dopamine metabolism. MPTP-induced cell loss in the substantia nigra was unaffected by nicotine treatment, indicating that nicotine acts at the striatal level to restore/maintain dopaminergic function. These data further support the possibility that nicotine contributes to the lower incidence of Parkinson's disease in smokers.
Quik
Maryka
M
The Parkinson's Institute, Sunnyvale, California, USA. mquik@parkinsonsinstitute.org
Parameswaran
Neeraja
N
McCallum
Sarah E
SE
Bordia
Tanuja
T
Bao
Shanshan
S
McCormack
Alison
A
Kim
Amy
A
Tyndale
Rachel F
RF
Langston
J William
JW
Di Monte
Donato A
DA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D008995:Monoamine Oxidase / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000201:enzymology; D009498:Neurotoxins; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism; D012453:Saimiri; D013378:Substantia Nigra / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015415:Biomarkers; D009498:Neurotoxins; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D004298:Dopamine