L-DEPRENYL CONFERS SPECIFIC PROTECTION AGAINST MPTP-INDUCED PARKINSONS DISEASE-LIKE MOVEMENT DISORDER IN THE GOLDFISH

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the goldfish causes a reversible, Parkinson's disease-like syndrome which includes loss of noradrenaline and dopamine from the brain, acc umulation of the toxic metabolite 1-methyl-4-phenylpyridinium species (MPP+), and substantial reduction in movement. L-Deprenyl, a selective monoamine oxidase-B inhibitor, protects the goldfish from loss of mov ement, but clorgyline, a selective monoamine oxidase-A inhibitor, has no such protective action. L-Deprenyl and clorgyline primarily inhibit goldfish brain monoamine oxidase-B and monoamine oxidase-A, respectiv ely. The mechanism by which MPTP causes reduced movement in goldfish i s to cause an increase in resting time. Otherwise normal average veloc ity occurred during periods of movement. L-Deprenyl protection results in entirely 'normal' levels of resting time and average velocity duri ng times of movement. Equivalent observations regarding l-deprenyl and clorgyline have been made in primate models of MPTP toxicity, and 1-d eprenyl is used for treatment of Parkinson's disease in humans. Theref ore it is suggested that the evolutionarily equivalent subcortical cir cuitry and neural density of the goldfish brain may provide a useful m odel upon which to search for drugs relevant to human Parkinson's dise ase.