The Effect Of Oxycodone On Cognitive Function And Klotho Protein Level In Rats

Objective:To investigate the effect of oxycodone (OXY) on cognitive function and klotho protein by conducting experiment on rats using different OXY dose regimen.Methods:Thirty, male SD rats were selected and randomly divided into five different groups: Group A (control group,0.9% normal saline 2ml/d), Group B (low stat OXY dose group, 0.25mg/kg), Group C (High stat OXY dose group,5mg/kg), Group D (increasing OXY dose regimen group,0.25-5mg/kg/d, for 7 days) and Group E (constant OXY dose regimen group, 2mg/kg/d, for 14 days). Morris Water Maze (MWM) task (7 days) was started. Rats were allowed to swim after one hour of intraperitoneal (i.p.) injection; normal saline 2ml/day for groups A, low and high dose OXY for group B and C respectively on first day of MWM task and rest other days with normal saline 2ml/day, OXY 0.25-5mg/kg/d for group D and OXY 2mg/kg/d for group E. Rats were then trained for 6 days in the place navigation test (PNT) and on the seventh day, the spatial probe test (SPT) was conducted by removing escape platform, then i.p. injections was stopped. A week later, PNT was conducted for the long term memory with the platform in its original position. During this period, data on escape latency, swim distance, crossing index and quadrant occupancy were recorded for every rat and was statistically analyzed. Klotho ELISA assay was conducted on blood samples collected after 24 hours of the last i.p. injection via vein of rats.Results:1. Single dose regimen:(1) PNT:When compared with the control group A, the average swimming distance and escape latency of group C were significantly higher (p<0.05), while there was no significant difference in group B (p>0.05); (2) SPT:While compared with group A, the crossing index and quadrant occupancy of group C rats were significantly decreased (p<0.05); (3) long-term memory in PNT:When compared with group A, the average of total swim distance and escape latency of group C was slightly increased but statistical significance was not established (p>0.05).2. Long term dose regimen:When compared to group A in PNT, the average swim distance and escape latency of group D was slightly increased with no statistical significance (p>0.05); in SPT, crossing index and quadrant occupancy of group D was slightly decreased compared to group A with no statistical significance (p>0.05).3. Comparing with that of control group, the expression of Klotho protein shows no significance difference (p>0.05).Conclusion:1. A single high dose of OXY can impair spatial learning and memory ability in rats but has less effect on long-term memory.2. Long-term administration of OXY has less effect on spatial learning and memory ability of rats; the constant dose of OXY is better than that of increasing doses of OXY.3. No significant correlation of cognitive dysfunction caused by OXY on Klotho protein.