PSYC 415 -- The Case of the Frozen Addict -- Handout on the video
(Nova, 2/18/86, copyright PBS)

I. drug-induced Parkinsonism
         A. synthetic heroin ("designer drugs") - at this time, small changes in
            the chemical structure of an illegal substance could make it a
            "street-legal" drug (this loophole in the law has since been
            plugged)
         B. treated with l-dopa (the standard treatment for Parkinson's disease)
               1. replaces missing dopamine in the brain (l-dopa is the
                  precursor for dopamine)
               2. without dopamine, thoughts of movement cannot be translated
                  into the movements themselves 
         C. contaminants in the synthetic drug (produced through sloppy basement
            chemistry) had destroyed the dopamine neurons in the substantia
            nigra, producing an advanced Parkinsonian state overnight
               1. MPPP (synthetic heroin)
                     a. injected rats freeze up
                     b. but only temporarily 
               2. MPTP (the contaminant)
                     a. injected rats are unaffected
                     b. injected monkeys develop Parkinsonism 
         D. revitalized research into Parkinson's disease 
II. Parkinson's disease
         A. a disease of old age characterized by:
               1. fine tremor, especially noticeable in the hands when at rest
               2. cogwheel rigidity
               3. difficulty initiating voluntary movements
               4. masked face
               5. shuffling gait 
         B. l-dopa therapy
               1. oftentimes must be taken every few hours even during the night
               2. side effects - writhing movements (athetosis) and
                  hallucinations; sometimes schizophreniform psychosis 
         C. severe cases (drug-induced) have been misdiagnosed as hysterical
            paralysis and as catatonic schizophrenia
         D. causes: environmental toxins are suspected
               1. substantia nigra cells die off gradually with aging
               2. if exposure to a toxin kills off large numbers of the cells,
                  then subsequent cell death with aging results in Parkinson's
                  disease
               3. 80% of nigral dopamine neurons must die before symptoms become
                  evident 
III. possible toxins
         A. MPTP is converted to MPP+ (Cyperquat) in the brain by MAO
         B. this product is related to chemical herbicides (Cyperquat, Paraquat)
         C. incidence of Parkinson's disease is highest in agricultural areas
            and areas with pulp and paper mills (according to a Canadian study
            cited in the video--a subsequent study done in the midwestern US has
            found the same pattern, but this study was not mentioned in the
            video)
         D. MPTP-like substances (pyridines) are widespread in the environment
         E. the MAO-blocking drug pargyline prevents the MPTP-induced
            Parkinsonism and prevents cell death in the substantia nigra
         F. PET scanning can detect those at risk for Parkinson's disease--
            someday it may be possible to do a routine brain scan on middle-aged
            people; those with abnormally low nigral cell counts may then be put
            on MAO blockers to prevent further nigral cell deterioration 
IV. some new findings since this video was made
         A. MPTP has become a major research tool in the study of Parkinsonism
            in animal models
         B. a Parkinsonian-like state has now been produced in rats
         C. some early research suggested that the toxin binds to a pigment
            molecule in the substantia nigra called neuromelanin (it is
            neuromelanin that gives the substantia nigra its dark appearance
            in primates; rats have very little pigmentation in the substantia
            nigra, which may be why they are less susceptible to the toxin)
         D. currently, research suggests that once MPTP passes the blood-brain
            barrier, it is taken up by glial cells, where monoamine oxidase
            (MAO) converts it to MPP+
               1. MPP+ is then taken up by dopamine neurons via the dopamine
                  transporter (reuptake mechanism)
               2. once in the cell it interferes with normal metabolism in the
                  mitochondria
               3. causes damage to mitochondrial DNA
               4. causes the build-up of reactive oxygen species (free radicals)
                  thus creating oxidative stress in the cell
               5. this triggers the caspase enzyme to initiate apoptosis
                  (commonly called cell suicide)
         E. the pesticide rotenone has a similar action in the brain and has
            been used to produce an animal model of Parkinsonism in rats