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This study assessed whether creatine could attenuate 3-nitropropionic acid (3NP)-induced neuropathological and behavioral abnormalities that are analogous to those observed in Huntington's disease (HD). Rats were fed diets containing either 1% creatine or normal rat chow for 2 weeks prior to the onset of 3NP administration, and for the duration of the study. 3NP was administered systemically in gradually increasing concentrations over an 8-week testing period. Results show that creatine can attenuate 3NP-induced striatal lesions, striatal atrophy, ventricular enlargement, cognitive deficits, and motor abnormalities on a balance beam task. Collectively, these findings indicate that creatine provides significant protection against 3NP-induced behavioral and neuropathological abnormalities and may have therapeutic potential for HD.