Phenytoin reverses the chronic stress-induced impairment of memory consolidation for water maze training and depression of LTP in rat hippocampal CA1 region, but does not affect motor activity

Previous studies have shown that phenytoin can protect hippocampal structure from damage by chronic stress, while whether it can reverse the hippocampal malfunction induced by chronic stress is unknown. We investigated the effects of phenytoin on motor activity of stressed rats and on the long-term memory of water maze spatial training, which is known to depend on hippocampal function. We also explored whether phenytoin could protect long-term potentiation (LTP) in hippocampal CA1 region from depression of chronic stressed rats. Isolated hippocampal slices of rats were used to observe the changes of LTP in hippocampal CA1 field with electrophysiological technique. The results showed that the motor activity of chronic forced-swimming rats was markedly higher than that of control rats, and phenytoin could not affect this change. The performance of water maze spatial training indicated that chronic stress damages long-term memory but not short-term memory, and phenytoin could reverse this long-term memory deficit. The increases of LTP after HFS in control and stress-phenytoin groups were significantly greater than those in stress-saline group (P < 0.05). There were no significant differences between control group and stress-phenytoin group (P > 0.05) and between control and control-phenytoin groups (P > 0.05). These findings provided the first evidence with behavioral and electrophysiological technique that phenytoin could reverse the hippocampal-dependent memory deficit and depression of LTP induced by chronic stress, which may be helpful for exploring the pathogenesis and improving the therapy of depression.