Effects of l‐Methyl‐4‐Phenyl‐l,2,3,6‐Tetrahydropyridine in the Dog

Effect of Pargyline Pretreatment

J. N. Johannessen, C. C. Chiueh, J. P. Bacon, N. A. Garrick, R. S. Burns, V. K. Weise, I. J. Kopin, Joseph E Parisi, S. P. Markey

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Abstract: Adult beagle dogs of either sex were injected with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐HCl (2.5 mg/kg, i.v.) alone or after pretreatment with pargyline (5.0 mg/kg, s.c, twice), with pargyline alone, or were unin‐jected. Groups were killed 2 h, 3 weeks, or 3 months after injection, and several brain areas were assayed for biogenic amines and their synthetic and degradative enzymes. MPTP caused a massive and permanent loss of striatal dopamine, tyrosine hydroxylase, and 3,4‐dihydroxyphenylalanine decarboxylase activities and the loss of cells within the substantia nigra pars compacta. Dopamine and norepinephrine also were depleted to various degrees in cortex, olfactory bulb, and hypothalamus; however, dopamine β‐hydroxylase activity in cortex was normal. There was no cell loss in the ventral tegmental area or locus ceruleus. The activities of monoamine oxidase (MAO)‐A and MAO‐B in cortex and caudate were not affected by MPTP. Despite a permanent loss of the ni‐grostriatal system, the dogs exhibited only a transient hypokinesia lasting 1‐2 weeks. Pargyline pretreatment prevented the loss of striatal dopamine and cells from the substantia nigra, but did not prevent a prolonged but reversible decrease in the concentration of dopamine metabolites. It is argued that this apparent inhibition of MAO is due not to suicide inactivation of the enzyme by MPTP, but to reversible inhibition by accumulation of the pyridinium metabolite, 1‐methyl‐4‐phenylpyridinium, selectively in aminergic terminals.

Original languageEnglish (US)
Pages (from-to)582-589
Number of pages8
JournalJournal of Neurochemistry
Volume53
Issue number2
DOIs
StatePublished - 1989
Externally publishedYes

Fingerprint

Pargyline
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine
Dogs
Corpus Striatum
Monoamine Oxidase
Metabolites
Hypokinesia
Ventral Tegmental Area
Biogenic Amines
Carboxy-Lyases
Locus Coeruleus
Olfactory Bulb
Tyrosine 3-Monooxygenase
Substantia Nigra
Enzymes
Mixed Function Oxygenases
Suicide
Hypothalamus
Brain

Keywords

  • 1‐Methyl‐4‐phenylpyridinium
  • Dog
  • l‐MethyI‐4‐phenyl‐l,2,3,6‐tetrahydropyr‐idine
  • Monoamine oxidase
  • Pargyline pretreatment

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Johannessen, J. N., Chiueh, C. C., Bacon, J. P., Garrick, N. A., Burns, R. S., Weise, V. K., ... Markey, S. P. (1989). Effects of l‐Methyl‐4‐Phenyl‐l,2,3,6‐Tetrahydropyridine in the Dog: Effect of Pargyline Pretreatment. Journal of Neurochemistry, 53(2), 582-589. https://doi.org/10.1111/j.1471-4159.1989.tb07373.x

Effects of l‐Methyl‐4‐Phenyl‐l,2,3,6‐Tetrahydropyridine in the Dog : Effect of Pargyline Pretreatment. / Johannessen, J. N.; Chiueh, C. C.; Bacon, J. P.; Garrick, N. A.; Burns, R. S.; Weise, V. K.; Kopin, I. J.; Parisi, Joseph E; Markey, S. P.

In: Journal of Neurochemistry, Vol. 53, No. 2, 1989, p. 582-589.

Research output: Contribution to journalArticle

Johannessen, JN, Chiueh, CC, Bacon, JP, Garrick, NA, Burns, RS, Weise, VK, Kopin, IJ, Parisi, JE & Markey, SP 1989, 'Effects of l‐Methyl‐4‐Phenyl‐l,2,3,6‐Tetrahydropyridine in the Dog: Effect of Pargyline Pretreatment', Journal of Neurochemistry, vol. 53, no. 2, pp. 582-589. https://doi.org/10.1111/j.1471-4159.1989.tb07373.x
Johannessen, J. N. ; Chiueh, C. C. ; Bacon, J. P. ; Garrick, N. A. ; Burns, R. S. ; Weise, V. K. ; Kopin, I. J. ; Parisi, Joseph E ; Markey, S. P. / Effects of l‐Methyl‐4‐Phenyl‐l,2,3,6‐Tetrahydropyridine in the Dog : Effect of Pargyline Pretreatment. In: Journal of Neurochemistry. 1989 ; Vol. 53, No. 2. pp. 582-589.
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AU - Chiueh, C. C.

AU - Bacon, J. P.

AU - Garrick, N. A.

AU - Burns, R. S.

AU - Weise, V. K.

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AU - Markey, S. P.

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