Effects Of Tramadol On Scopolamine-induced Impairment Of Spatial Working Memory In Rats

Objective: In recent years, with the progress of anesthesia technology, innovation of new anesthetics, as well as the continuous improvement of monitoring tools makes anesthesia mortality significantly reduced. The focus on clinical anesthesia has shifted to reduce the incidence of heart、brain and other body organs complications. Elderly patients who accept major surgery are increased, as China entered the aging society stage, resulting in a considerable portion of patients with postoperative mental dysfunction, manifested as stroke(1.5~5.2%), delirium(10~30%), short-term(33~83%) and long term(20~60%) of cognitive dysfunction[1]. Postoperative Cognitive Dysfunction(POCD) is greatly concerned for its high incidence and great harm to the prognosis of patients. Scholars, domestic and foreign, have done a lot of research for it, but the pathogenesis of POCD is still unclear, so it’s lack of effective control methods in the clinic. With the progress of research in neurobiology, the current view is that the physiological function of central acetylcholine is related to learning, memory, pain, sleeping, feeling and movement, whereas the neurotransmitters which is involved in mental and emotional activity mainly distributed in the central Monoamine gray matter, the hypothalamus and the edge of the cortex neurotransmitter systems, including dopamine(DA), 5-hydroxytryptamine(5-HT) and norepinephrine(NE) [2]. The relationship between monoamine neurotransmitters and POCD, which have variety of different causes, has been reported both in China and abroad. Therefore, this study is to observe the preventive effect on cognitive dysfunction in rats by intraperitoneal injection of 5-HT reuptake inhibitors tramadol, to verify that scopolamine cognitive dysfunction of rats is linked with certain neurotransmitters and to explore the possible mechanism of POCD disease.Method: 1 Healthy 2-month-old male SD rats, weighing 130 ~ 150 g, are randomly divided into four groups(n=10): saline control group(group C), scopolamine group(group S), tramadol group(group T) and tramadol intervention group(group S + T). Group S inject scopolamine 1.8 mg/kg intraperitoneally. Group C and group T are intraperitoneally injected with equal volume saline or tramadol 10 mg / kg, Group S + T are injected with scopolamine 1.8mg / kg and tramadol 10 mg / kg. 2 After injection of drugs, putting the four groups rats into the homemade box for open-field test immediately, then to observe emotional and behavioral changes of rats in the first 10 min and within 1h after injection. To record the number of cells that rats ran around in each time period(T0-T6) and the number of times in vertical exploratory behavior, as well as the residence time in the central cells, the number of running in the central cells, the number of groomings and the time of grooming. 3 The rats in four groups test the cognitive function by Y-maze test after injecting drug 7 days, to record the number of total training and standard time. 4 The rats are anesthetized by Intraperitoneal injecting chloral hydrate 350 mg/kg, then taking the eyes blood 2ml, to decapitate, taking bilateral hippocampal neurons after the Y-maze test. 5 BY observing pathological HE staining in hippocampus.ultrastructure of hippocampal neurons to learn ultrastructure of hippocampal neurons. 6 To detect the level of 5-HT in serum and hippocampal neurons by ELISA. 7 Data are analyzed by using SPSS17.0 software, measurement data as mean ± standard deviation( sx ±), the repeated measurement data using repeated measures analysis of variance, the randomized block data using oneway ANOVA, SNK test count data, P<0.05 was considered statistically significant.1 Under the light microscope, the hippocampal neurons cells of group C and T are arranged regularly, clear, with rounded and big nucleus, with regular cell shape. The hippocampal neurons cells of group S is disorganized and the structure is unclear, the cell membrane has disrupted, cytoplasm has decreased, karyopyknosis and vacuolar degeneration. The morphological changes of hippocampal neurons cells in group S+T rates are significantly reduced compared with group S. 2 Comparing with group C, in group S the number of surrounding cells running of rats in open field test, the number of vertical movement and central cells running has increased, central cells stay longer, groomings less in each time period. The time of grooming has shortened in the T1、T2 and T6 period. The number of total training and standard time has increased, and the level of 5-HT in serum and hippocampus neurons has increased in Y-maze test(P<0.05);The difference, in which the number of surrounding cells running and vertical movement, the time of central cells staying, grooming’s number and time, is not statistically significant between group S+T and group C in each time period(P>0. 05). In group S+T, The number of total training and standard time has increased, and the level of 5-HT in serum and hippocampus neurons has increased in Y-maze test(P<0. 05). Compared with group S, the number of surrounding cells running, vertical movement and central cells running has increased, the time of central cells staying has shortened, groomings more, and the time of grooming has prolonged in T1 period in group S+T in open field test. The number of total training and standard time has reduced, and the level of 5-HT in serum and hippocampus neurons has increased in Y-maze test(P<0.05).All these indicators of cognitive function was no significant difference between groups C and T rats(P> 0. 05). Results:Conclusion: Intraperitoneal injection of tramadol 10 mg / kg for rat can reduce the performance of cognitive dysfunction which caused by copolaminein, so that the morphological changes in hippocampal neurons can be decreased, the level of 5-HT in serum and hippocampus neurons can beelevated. Suggesting that the model of cognitive dysfunction may be related to the imbalance between the equilibrium of acetylcholine and 5-HT in rats.