Thesis Title

Effects of Central and Peripheral Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (Mptp) in the Rat and Mouse

Date of Graduation

Fall 1986

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Russell Rhodes

Subject Categories

Biology

Abstract

MPTP has been observed to cause irreversible symptoms of parkinsonism associated with selective degeneration of the substantia nigral dopamine neurons in the midbrain of man and monkeys. Although rodents are less sensitive to the neurotoxic action of MPTP, it has been found that central catecholaminergic neurons in mice are damaged following systemic adminstration of large doses of MPTP. Following adminstration: 1) MPTP is taken up by monamine oxidase containing glial cells and converted to its neurotoxic form N-methyl-4-phenyl pyridinium ion (MPP+), and 2), this is followed by uptake of MPP+ by dopaminergic cells via an uptake system. The above two steps are necessary for the neurotoxicity of MPTP to be exhibited. To determine whether direct intranigral injection of MPTP would induce any neuro-toxic effects or locomotor disturbance in the rat, Sprague-Dawley rates with 26 gauge implanted cannulae received Several injections of MPTP or MPP+. One week later they received a single injection of amphetamine which caused ipsilateral rotation. The unilateral distruction of the dopaminergic neurons of rates leads to asymmetric locomotor behavior when followed by a dopamine releasing agent such as D-Amphetamine. The depletion of striatal dopamine and norepinephrine by MPTP was also investigated in mice. This neurotoxicity was prevented by pretreatment with either Deprenyl (a monoamine oxidase type B inhibitor), or Mazindol ( a dopamine reuptake inhibitor). These results support that MPTP exerts its neurotoxicity does not seem to be specific to dopaminergic cells; norepinephrine was depleted as well. These small animal models should facilitate further studies on various aspects of MPTP neurotocixity.

Copyright

© Leila T Najafi

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