Intracerebroventricular (ICV) administration of ouabain to rats induces motor hyper- and hypoactivity that have been hypothesized to model the mania and depression of bipolar illness, respectively. The extent of ouabain-induced change in activity may vary according to the test environment. To determine the degree of differential response to ICV ouabain in the open field and automated activity monitors, the authors examined a large number of animals (n=40) in both environments. ICV ouabain produced a four-fold increase in open field activity versus ICV artificial cerebrospinal fluid (aCSF) (mean +/- SD: 258.7 +/- 316.61 vs. 84.8 +/- 86.16 squares traversed) (t = 2.648, P = 0.011), but did not alter horizontal activity in automated activity monitors (8193.5 +/- 4902.52 vs. 7088.47 +/- 3046.85 beam interruptions) (t = 0.847, P = 0.4). This increase in activity persisted for at least one week (161.0 +/- 186.35 for ICV ouabain vs. 46.1 +/- 47.46 for ICV aCSF, P = 0.065). Open field is superior to automated activity monitors in capturing ouabain-induced hyperlocomotion response.