Dissociating effects of spatial learning from locomotor activity for ouabain-induced bipolar disorder-like rats

Whether ouabain, a Na+- and K+-activated adenosine triphosphatase inhibitor, mimics cognitive impairments that can be dissociated from motor effects in the bipolar disorder-like animal model remains unclear. Ouabain and the vehicle aCSF were microinjected into the left lateral ventricle immediately, after 4 h, and after 24 h. The results showed that (a) locomotion responses of the Immediate group were significantly decreased compared to those of the aCSF group, particularly the first five minutes. (b) The ouabain-treated rats have longer latency and total distance traveled in the water maze task; however, the velocity was not affected for the ouabain group. (c) The analysis of covariance showed that the latency time (but not the total distance traveled and velocity) of the ouabain group was more impaired than that of the aCSF group, regardless of omitting total distance traveled and cross movement in the open field test. The latency might be more sensitive than the distance traveled and the velocity for assessing spatial learning. Dissociating the spatial learning from the movement may allow testing drug treatments of cognitive deficits independent of locomotor effects associated with bipolar disorder.