RT Journal Article SR Electronic T1 Dopamine Depletion Does Not Protect against Acute 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Toxicity In Vivo JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 9428 OP 9433 DO 10.1523/JNEUROSCI.0130-05.2005 VO 25 IS 41 A1 Daphne M. Hasbani A1 Francisco A. Perez A1 Richard D. Palmiter A1 Karen L. O'Malley YR 2005 UL http://www.jneurosci.org/content/25/41/9428.abstract AB Dopamine (DA) has been postulated to play a role in the loss of dopaminergic substantia nigra (SN) neurons in Parkinson's disease because of its propensity to oxidize and form quinones and other reactive oxygen species that can alter cellular function. Moreover, DA depletion can attenuate dopaminergic cell loss in vitro. To test the contribution of DA to SN impairment in vivo, we used DA-deficient mice, which lack the enzyme tyrosine hydroxylase in dopaminergic cells, and mice pharmacologically depleted of DA by α-methyl-p-tyrosine pretreatment. Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that produces parkinsonian pathology in humans, nonhuman primates, and rodents. In contrast to in vitro results, genetic or pharmacologic DA depletion did not attenuate loss of dopaminergic neurons in the SN or dopaminergic neuron terminals in the striatum. These results suggest that DA does not contribute to acute MPTP toxicity in vivo.