The phosphodiesterase-4 inhibitor Ro 20-1724 reverses learning and memory impairments, and downregulation of CREB in the hippocampus and cortex induced by ketamine anesthesia in immature rats.

AIM: The objective of the study was to examine the effects and possible mechanisms of phosphodiesterase-4 inhibitor Ro 20-1724 on learning and memory impairments induced by ketamine anesthesia. Further, expression the cAMP response element binding proteins (CREB), transcription factors involved in long-term memory, were analyzed in conjunction with these effects of Ro 20-1724. METHODS: Ninety-six immature (21-day-old) Sprague-Dawley rats were divided into eight groups. To assess the learning and memory impairments, Morris Water Maze task was used. Expression of total and phosphorylated CREB in the hippocampus and cerebral cortex was evaluated by Western blot. RESULTS: THE escape latency and frequency of passing the platform in Morris Water Maze task were markedly longer after ketamine anesthesia. However, treatment with Ro 20-1724 significantly (P<0.05) improved both learning and memory performance. Further, administration of Ro 20-1724 reverted the down-regulation of total and phosphorylated CREB caused by ketamine (P<0.05), as demonstrated by Western blot analysis of CREB expression in the hippocampus and cortex. CONCLUSION: Treatment with Ro 20-1724 improves learning and memory deficits caused by ketamine anesthesia in immature rats, possibly via increases in expression of total and phosphorylated CREB in the hippocampus and cerebral cortex.