The neurotoxican cuprizone (CPZ, a copper chelator) has been used extensively to create a mouse model of demyelination. However, the effects on behavior of CPZ treatment have not been reported in C57BL/6 mice given a diet containing 0.4% CPZ within 3 weeks. Behavioral abnormalities were assessed using a range of test: Y-maze, spontaneous locomotor activity, rota-rod test, novel object recognition, climbing. Mice exposed to CPZ displayed more arm entrance, locomotor movements, and climbing behavior, suggesting an increase in central nervous system activity. However, no significant differences either in spontaneous alternation or latency to fall from the rotating drum were observed, demonstrating that spatial working memory or motor coordination and balance didn’t impair by CPZ short-term exposure. In addition, they showed higher dopamine levels and dopamine transporter expression in the cortex. Our findings indicate that increased central dopaminergic activity may relate to the behavioral abnormality in mice, and this CPZ short-term exposure with higher dose may offer a model to study some aspects of biology relevant to schizophrenia and other related disorders.