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

Clin Investig. Mar-Apr 1992;70(3-4):232-8. doi: 10.1007/BF00184656.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / antagonists & inhibitors
  • 3,4-Dihydroxyphenylacetic Acid
  • Animals
  • Dopamine / metabolism
  • Drug Tolerance
  • Homovanillic Acid / metabolism
  • Infusion Pumps
  • MPTP Poisoning*
  • Male
  • Mecamylamine / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Nicotine / administration & dosage
  • Nicotine / pharmacology*
  • Parkinson Disease, Secondary / chemically induced*
  • Parkinson Disease, Secondary / pathology
  • Parkinson Disease, Secondary / prevention & control
  • Receptors, Nicotinic / drug effects*
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology*

Substances

  • Receptors, Nicotinic
  • 3,4-Dihydroxyphenylacetic Acid
  • Mecamylamine
  • Nicotine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine
  • Homovanillic Acid