Effects of phosphodiesterase-4 inhibitor Ro 20-1724 on learning and memory function after ketamine anesthesia and cAMP/PKA-CREB-BDNF signal pathway in immature rats

Objective To observe a new phosphodiesterase-4 inhibitor Ro 20-1724 on ketamine anesthesia-induced learning and memory impairment and cAMP/PKA-CREB-BDNF signal pathway in immature rats. Methods Twenty-four 21 day-old SD rats were randomly divided into 4 groups(n=6 each): control group(group C); ketamine group (group K); ketamine+ Ro 20-1724 group(group K+ Ro) and ketamine+ vehicle (0.1% ethanol) group (group K+ E). Ketamine 70 mg/kg was injected intraperitoneally(IP) once a day for 7 consecutive days in groups K, K+ Ro, and K+ E.Ro 20-1724 0.5 mg/kg and equal volume of vehicle were injected IP at 30 min after IP ketamine each time respectively. Morris water maze was used to assess learning and memory ability after 2 days normal feeding, the escape latency and frequency of passing the platform were recorded. The animals were killed after water maze test and the cAMP, PKA, p-CREB, and BDNF protein expression in hippocampus were detected. Results Repetitive ketamine anesthesia significantly prolonged the escape latency(P 0.05). Conclusion ketamine anesthesia-induced learning and memory impairment can be improved by Ro 20-1724, and cAMP/PKA-CREB-BDNF signal pathway in hippocampus participated in the changes. Key words: Ro 20-1724; Ketamine anesthesia; Immature rats; Cognitive function