Effects Of Hydrogen Sulfide And Nitric Oxide On The Learning And Memory Of Heroin-addictive Rats

Objective:To observe the effects of hydrogen sulfide(H₂S) and nitric oxide(NO) on the learning and memory of heroin-addictive rats.Methods:Fifty-two male SD rats were randomly divided into four groups:control group,Heroin group(experimented 1 group),Heroin+HA group(experimented 2 group) and Heroin+NaHS group(experimented 3 group).Except for control group,heroin was injected subcutaneously twice a day for nine days according to the principle of daily increasing dose in other groups.Control group only received normal saline in the same way.HA was injected intraperitoneally before injecting heroin everyday(0.5mmol/kg),and NaHS was injected in the same way(0.09mmol/kg).On the tenth day,the withdrawal symptoms precipitated by naloxone were evaluated.After continuing injecting heroin for five days,the ability of spacial learning and memory was tested by Morris water maze.To observe the hippocampal morphology by hematoxylin and eosin stain under optical microscope.The plasma and hippocampus level of NO and H₂S were detected by the spectrophotometer method.The expression of CBS mRNA and nNOS mRNA was observed by Real time PCR.Results:1) The withdrawal symptom scores of experimented 1,2,3 group were higher than control group(P＜0.05).But compared with experimented 1 group,the withdrawal symptom scores of experimented 3 group were lower (P＜0.05).2) Compared with control group,the mean escape lantency in place navigation test prolonged(P＜0.01),the mean exploring time in original platform quadrant in spacial probe test shortened(P＜0.01) in experimented 1,2,3 group,the percentage of swimming distance in original platform quadrant and times of passing plateform were less(P＜0.01) in experimented 1,2 group.Compared with experimented 1 group,the mean escape lantency shorten(P＜0.01),the mean exploring time in original platform quadrant prolonged(P＜0.01),the percentage of swimming distance in original platform quadrant(P＜0.01) and times of passing plateform(P＜0.05)were more in experimented 3 group.3) Compared with control group,the plasma level of NO was elevated(P＜0.01),NO in hippocampus was elevated(P＜0.05) while H₂S of hippocampus decreased(P＜0.01) in experimented 1,2,3 groups,the plasma level of H₂S decreased(P＜0.01),the expression of nNOSmRNA and CBSmRNA up-regulated(P＜0.05) in experimented 1,2 group.Compared with experimented 1 group,NO in plasma and hippocampus decreased(P＜0.01) while H₂S was elevated(P＜0.01),the expression of nNOSmRNA and CBSmRNA down-regulated in experimented 3 group and the expression of CBSmRNA down-regulated(P＜0.05) in experimented 2 group.4)Neuronal degeneration and necrosis in hippocampus tissue were observed in experimented 1,2,3 group.But Neuronal degeneration and necrosis in hippocampus were more remarkable in experimented 1 group than that in experimented 3 group.Conclusion:1) Heroin-addiction can injure hippocampus tissue and impair the ability of learning and memory in SD rats.2) Heroin-addiction can elevate NO level in plasma and hippocampus while decreaseing H₂S level in rats.3) Exogenous H₂S donor NaHS can reduce the impairment of ability of learning and memory,alleviate the withdrawal symptoms,inhibit the production of NO and down-regulate the expression of nNOSmRNA.