Chronic treatment with mood stabilizer lithium inhibits amphetamine-induced risk-taking manic-like behaviors

A lack of behavioral tests and animal models for manic-depressive bipolar disorder is recognized as an important factor limiting development of novel pharmaceutical treatments for the disorder. Repeated amphetamine-induced hyperactivity is a commonly used animal model for mania. However, hyperactivity represents only one facet of mania and is also seen in other disorders. Increased engagement in risk taking behavior is frequently observed in the manic phase of bipolar disorder. In the present study, we analyzed the effect of the most commonly used mood stabilizer lithium on repeated amphetamine treatment-induced risk-taking behaviors in rats using elevated plus maze and wire-beam bridge tests. We found that repeated amphetamine treatment not only increased locomotor activity, but also increased risk taking behaviors in rats, and further that chronic lithium treatment inhibited the amphetamine-increased risk taking behavior. Our studies suggest that these tests may be useful tools to analyze the pharmacological validity of new and improved anti-manic drugs in animals.