Effects of RO20-1724 on repetitive ketamine administration-induced learning and memory impairment in immature rats

Objective To investigate the effects of RO20-1724 on repetitive ketamine administration-induced learning and memory impairment in immature rats.Methods Forty-eight 21-day-old SD rats of both sexes weighing 45-55 g were randomly divided into 4 groups (n =12 each):control group(group C); ketamine group (group K); ketamine + RO20-1724 group (group K+ R) and ketamine + vehicle (ethanol) group (group K+ A).Ketamine 70 mg/kg was injected intraperitoneally (IP) once a day for 7 consecutive days in groups K,K+ R and K+ A.RO20-1724 0.5 mg/kg and equal volume of ethanol were injected IP at 30 min after IP ketamine once a day for 7 consecutive day in groups K + R and K + A respectively.Morris water maze test was used to assess learning and memory ability.The escape latency and the number of times of passing the safe zone were recorded.The animals were killed after water maze test and their brains removed for microscopic examination of hippocampus and determination of p-CREB protein expression in hippocampus (by Western blot).Results Repetitive ketamine administration significantly prolonged the escape latency,decreased the number of times of passing the safe zone and down-regulated the expression of p-CREB protein in hippocampus on the 3rd and 4th day in group K as compared with group C.RO20-1724 significantly attenuated the above changes induced by repetitive ketamine administration in group K + R as compared with group K.Electron microscopic examination showed that RO20-1724 significantly ameliorated repetitive ketamine administration-induced hippocampal neuronal damage.Conclusion RO20-1724 can ameliorate cognitive dysfunction induced by repetitive ketamine administration.Up-regulation of cAMP /CREB signaling pathway is involved in the mechanism. Key words: Phosphodiesterase inhibitors;  Ketamine;  Cognition disorders;  Minors