The 3-NP Model of Striatal Neurodegeneration

The mitochondrial toxin 3-nitropropionic acid (3-NP) is an irreversible inhibitor of respiratory chain complex II. Chronic systemic administration of 3-NP to mice, rats, and non-human primates leads to preferential degeneration of the striatum, and produces motor and cognitive symptoms that are highly reminiscent of Huntington's disease (HD). HD is caused by a dominant inherited expansion of CAG repeats in the Huntington gene. Thus, many aspects of HD cannot be mimicked by 3-NP. However, recent research shows that mitochondrial defects and oxidative stress may play a key role in HD pathogenesis, further supporting the potential utility of the 3-NP model of striatal degeneration. First, a basic protocol to produce acute striatal lesions in rats using repeated intraperitoneal injection of 3-NP is described. Second, a more complex protocol that takes advantage of the use of osmotic minipumps to steadily release 3-NP leading to consistent lesions and motor symptoms in Lewis rats is presented.