Electrophysiological and neurochemical correlates of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in the mouse

G. Jonsson, E. Sundström, I. Mefford, L. Olson, Steven Johnson, R. Freedman, B. Hoffer

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an agent which produces a parkinsonian syndrome in man. To explore the use of MPTP in a rodent model of parkinsonism, male albino mice (NMRI) were given MPTP (50 mg/kg, s.c.) twice with a 6-8 h interval. Up to 10 weeks after injection, mice were killed and high-pressure liquid chromatography was used to assay dopamine (DA) and noradrenaline (NA) concentrations in various regions of the CNS. At 4 and 10 weeks after injection, DA levels were significantly reduced in occipital cortex (-40%), hippocampus (-30%), and striatum (-60%). NA levels were reduced by 60-80% in frontal and occipital cortex, hippocampus, and cerebellum. Neither DA nor NA concentration was reduced in spinal cord. Dopaminergic denervation was also suggested by electrophysiological data which showed that treatment with MPTP increased the spontaneous discharge rate of caudate neurons and decreased the potency of locally administered phencyclidine, an indirect DA agonist. However, denervation was evidently not complete enough to produce postsynaptic receptor supersensitivity, as MPTP treatment did not increase the potency of locally applied DA, and it did not increase 3H-spiperone binding in striatal membrane preparations. These results suggest that MPTP causes regionally selective and long-term reductions of catecholamine transmission in the CNS of the mouse.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume331
Issue number1
DOIs
StatePublished - Oct 1 1985
Externally publishedYes

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Catecholamines
Neurons
Dopamine
Occipital Lobe
Norepinephrine
Parkinsonian Disorders
Denervation
Hippocampus
Corpus Striatum
Spiperone
Phencyclidine
Injections
Dopamine Agonists
Frontal Lobe
Cerebellum
Rodentia
Spinal Cord
High Pressure Liquid Chromatography
Membranes

Keywords

  • Catecholamines
  • Electrophysiology
  • MPTP
  • Parkinson's disease
  • Striatum

ASJC Scopus subject areas

  • Pharmacology

Cite this

Electrophysiological and neurochemical correlates of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in the mouse. / Jonsson, G.; Sundström, E.; Mefford, I.; Olson, L.; Johnson, Steven; Freedman, R.; Hoffer, B.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 331, No. 1, 01.10.1985, p. 1-6.

Research output: Contribution to journalArticle

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