1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces lesions in the substantia nigra of the cat which are visible by nuclear magnetic resonance imaging (MRI)
Male cats aged 6-8 months were administered two doses of MPTP (10 mg/kg) ip in saline 48 hrs apart. The cats exhibited drooling, dilation of pupils, incontinence, heightened sensitivity to touch and light, hypo- and bradykinesia and ataxia. After the second injection marked rigidity was observed, especially in the hind limbs. The cats were anesthesized and imaged with a 1.5%T MR imager using a spin-echo sequence with TR 2500ms and Te 25ms. MRI showed an increase in signal intensity extending from the periaqueductal grey matter through the region of the substantia nigra. Further an acute decrease in the differentiation of white and grey matter was observed. This is commonly associated with generalized cerebral edema. Measurement of striatal biogenic amine contents showed 20-30% decreases in striatal dopamine, 77% decreases in DOPAC, and 73-80% decrease in HVA. The content of the serotonin metabolite 5-hydroxyindoleacetic acid was unchanged indicating that the toxic effects are specific to dopaminergic neurons. Pathological examinations of the brains showed no macro or microscopic changes. These findings could represent the first observation of the actual processes involved in the degeneration of dopaminergic neurons in Parkinsonism.
- Research Organization:
- Ohio State Univ., Columbus
- OSTI ID:
- 7186643
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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TOXICITY
CATS
DOPAMINE
NERVES
NUCLEAR MAGNETIC RESONANCE
SPIN ECHO
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AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
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CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
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DRUGS
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HYDROXY COMPOUNDS
MAGNETIC RESONANCE
MAMMALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PHENOLS
POLYPHENOLS
PYRIDINES
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SPECTRA
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