From Drugs of Abuse to Parkinsonism: The MPTP Mouse Model of Parkinson’s Disease - Drugs of Abuse: Neurological Reviews and Protocols - page 101

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From Drugs of Abuse to Parkinsonism:
The MPTP Mouse Model of Parkinson's Disease
Yuen-Sum Lau and Gloria E. Meredith
1. Introduction
It began with a single case of drug abuse in Maryland (1) , followed by
four reported cases in California (2) in which young heroin addicts self-
injected homemade “synthetic heroin” analogs contaminated with an impure
chemical byproduct, 1-methyl-4-phenyl-1,2,3,6-tetrahydroperidine (MPTP),
and consequently they developed severe Parkinson-like syndrome. These cases
were considered extremely unusual, as Parkinson's disease (PD) is a slow,
progressive, neurodegenerative disorder normally affecting older patients, with
the age at onset for the majority during the 60s. It was quickly determined
that MPTP is a potent neurotoxic agent that selectively destroys the central
dopaminergic neurons, creates a defi cit in dopamine transmission, and results in
neurological symptoms indistinguishable from those of classical PD. Idiopathic
PD patients and MPTP-intoxicated individuals all exhibit the cardinal signs of
bradykinesia, rigidity, resting tremor, and gait disturbance (3 , 4) . With such an
important discovery, MPTP has been widely used in various types of in vitro
and in vivo models for elucidating possible pathophysiological mechanisms
and for exploring new therapeutic and neuroprotective approaches hoping to
slow the disease process and/or reverse the debilitating symptomology of the
disease. A recent survey of Medlines showed that publications involving MPTP
research have steadily increased since 1983 ( Fig. 1 ).
2. Neurologic Findings in PD
Although PD was fi rst described in 1817, very little is known about its
etiology. On a neuroanatomical basis, it is clear that dopaminergic neurons