Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle

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Abstract
Defects in the ubiquitin‐proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z‐lle‐Glu(OtBu)‐Ala‐Leu‐al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 μl of 70% ethanol over a 2‐week‐period. We found significant decreases in nigrostriatal dopamine in PSI‐treated mice compared with saline‐treated mice. However, we observed similar decreases in the ethanol‐treated vehicle control group. Administration of ethanol alone led to significant long‐term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model. © 2006 Movement Disorder Society