Effect Of Fentanyl Clinical Application On Learning And Memory Related Signal Pathway In Hippocampus

Learning and memory is one of the most complex physiological activities in organism, and the brain adjusts this process through many mechanisms. In these mechanisms, the very protein and signal pathway play significant roles. However, anesthesia would cause lost in memory to some extent, and even lead to memory disorder disease. Fentanyl, a synthetic anesthesia and a kind of μ opioid receptor agonist, is widely clinically used because of its efficiency. So far, no specific difference about anesthesia of sedative dose has been reported. This issue studied the effect of sedative dose Fentanyl on short-term memory, in order to clarify its mechanism and provide theoretical basis for its proper utility.This experiment used Wistar male rats as subjects, choose 5 random Ly from 20 as normal saline control group, and the rest as treatment group. Firstly, a 5-day water maze place navigation was conducted. In the former 4 days rats were trained the 4 times per day, 2 times in the morning and 2 times in the afternoon, respectively, 90 seconds each time. In the 5th day, intraperitoneal injection equivalent dose normal saline and sedative dose Fentanyl 20μg/kg(0.4m L/kg), proceed this step after injection 10min、6h、24h, respectively, and record the escape latency. But the rats were sedative in 10 min, unavailable to test, so directly pick hippocampus for further use. Right after each water maze test, hippocampus was picked and stored under-80℃, and then the protein express difference of ARC、CREB、p-CRED、ERK and p-ERK in hippocampus were determined by Western Blot, and the change of ARC、CREB、ERK mRNA in hippocampus were determined by RT-PCR, so that the effect of the drug on ERK signal could be inferred.10min after administration, no remarkable difference of Arc protein expression from the control group was observed, while CREB、p-CREB、ERK and p-ERK protein expression increased.6h after administration, protein expression was obviously lower than the 10 min group, and slightly lower than the control group, but the phosphorylated ERK slightly higher than the control group.24 h after administration, all the protein expression except Arc decrease dramatically against normal saline control group. Meanwhile, the result of real-time PCR showed that the trends of CREB、ERK mRNA in each period coincide with the protein expression in Western Blot, which proved the experiment result.Morris water maze experiment proved that fentanyl in rats with a single injection sedative amount(20μg/kg) from the behavior perspective embody the effect on learning and memory. While corresponding protein level determined by real-time PCR and Wester blot implied that injectionsedative dose may eventually decrease the expression of relative gene and effect learning and memory.