Effects of lithium and carbamazepine on spatial learning and depressive behavior in a rat model of bipolar disorder induced by ouabain

Abstract Lithium (LiCl) and carbamazepine (CBZ), the common mood stabilizers, are thought to be effective treatments for bipolar disorder. The aim of the present study was to investigate whether LiCl as well as CBZ has similar effects on the bipolar disorder-associated cognitive dysfunctions in rats, particularly the spatial learning and depressive responses. Adult male Wistar rats were administered intracerebroventricularly with 5 μl of 10 − 3  M ouabain on session 1, and then received an intraperitoneal injection of LiCl or CBZ for 4 sessions (1 session/2 days). For the behavioral tests, all rats were subjected to the water maze 15 min for spatial learning and the forced swimming test 5 min for depression on each session. The present results showed that ouabain resulted in increased latency and longer distance traveled to reach the hidden platform in the water maze, indicating that ouabain impaired the spatial learning. However, ouabain did not affect swimming velocity in the water maze and depressive responses in the forced swimming test. LiCl treatment decreased the ouabain-enhanced latency and the total distance, but not the velocity, swam to reach the hidden platform in the water maze task. Additionally, LiCl did not result in changes of any depressive indices, such as struggling behavior, swimming behavior, and floating behavior. Likewise, CBZ did not affect any behavioral indices of spatial learning and depression. A linear regression analysis suggested that LiCl, but not CBZ, could predict the decreased latency and total distance traveled except the velocity of swimming in the water maze and depressive behaviors. In summary, the present results suggested that lithium provided a better therapeutic effect than CBZ for ouabain-caused dysfunctions of spatial learning in a rat model of bipolar disorder.