Ro 20-1724 Ameliorates Learning Deficit and Long-Term Memory Impairment Secondary to Repeated Ketamine Anesthesia in Young Rats

To investigate effects and possible mechanism of Ro 20-1724, a PDE4 inhibitor, on long-time learning and memory ability following repeated ketamine exposure in immature rats. Methods: Sixty 21-day-old SD rats were randomly divided into five groups (n = 12): C: Normal control group, S: Saline control group, K: Ketamine, K + Ro: Ketamine + Ro 20-1724, K + E: Ketamine + ethanol vehicle. Ro 20-1724 (0.5 mg·kg) or its vehicle (ethanol) was administered intraperitoneally 30 minutes after ketamine anesthesia (70 mg·kg), daily for seven days. Nine weeks after birth, the Morris water maze was used to test the ability of learning and spatial localization memory on the rats. Following behavioral testing, animals’ hippocampi were removed for Western blot and electron microscopic examination. Results: In the Morris water maze test, compared with controls, the escape latency in groups exposed to ketamine or ketamine plus the ethanol vehicle were significantly prolonged (P < 0. 05), the ability of spatial localization was lower (P < 0.05), and the expression of p-CREB in the hippocampus was also decreased (P < 0.05), while there was no significant difference between control groups and animals treated with Ro 20-1724 following ketamine exposure (P > 0.05). Electron microscopy demonstrated degenerative changes in hippocampal neurons of animals repetitively exposed to 70 mg·kg Ketamine, which was ameliorated by Ro 20-1724 (0.5 mg·kg). Conclusion: The PDE-4 inhibitor Ro 20-1724 (0.5 mg·kg) reverses cognitive deficits associated with repeated ketamine exposure in young rats, most likely via increased cAMP/CREB signaling in the hippocampus and preservation of hippocampal neuronal ultrastructure.