Differential effects of acute and chronic nicotine treatment on MPTP-(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced degeneration of nigrostriatal dopamine neurons in the black mouse.
Evidence exists for a negative correlation between Parkinson's disease and smoking. The present and previous studies indicate that nicotine treatment can markedly alter the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in the black mouse based on biochemical determinations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in neostriatum and substantia nigra 2 weeks after MPTP injection. Acute intermittent treatment with (-)nicotine starting 10 min before the MPTP injection partly protected against MPTP-induced neurotoxicity in the neostriatum and substantia nigra. Also, a partial protection was observed in the substantia nigra when (-)nicotine was given together with MPTP in an acute intermittent treatment schedule. Conversely, chronic infusion of (-)nicotine via minipumps produced a dose-related enhancement of MPTP-induced DA neurotoxicity in the neostriatum. It is suggested that the protective activity of nicotine in the MPTP model is related to a blockade of MPP+ uptake into the DA cells via increased DA release. Conversely, the nicotine enhancement of MPTP-induced DA toxicity is suggested to be caused by a failure of the nicotinic cholinoceptors to desensitize to the chronic (-)nicotine exposure, leading to increased chronic influx of Na+ and Ca2+ ions via the ion channels of the nicotinic cholinoceptors located on the DA neurons with associated increased Ca ion toxicity and increased energy demands.
Janson
A M
AM
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm.
Fuxe
K
K
Goldstein
M
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004361:Drug Tolerance; D006719:Homovanillic Acid / Q000378:metabolism; D007260:Infusion Pumps; D020267:MPTP Poisoning; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*
D011978:Receptors, Nicotinic; D015102:3,4-Dihydroxyphenylacetic Acid; D008464:Mecamylamine; D009538:Nicotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid