Hydrogen Sulfide Enhance Morphine Dependent Rats' Learning And Memory Capacity And Affect The Hippocampus' CAMP Signaling Pathway

Objective: As a novel type of endogenous neuron gaseous mediator, H2 S plays an important role in the regulation of the central nervous system. H2 S can adjusting the AC/c AMP/CREB signaling pathway and improve the dysfunction of cognition, learning, memory, caused by diseases of nervous system.This experiment focused on exploring whether the H2 S can regulate cognitive dysfunction related to morphine addiction rat by influencing the adenylate cyclase pathway in the hippocampus of morphine addiction rat?Methods: In accordance with the principle of dose increasing day by day,to establish animol model of chronic morphine addiction via hypodermic injection on the back with morphine hydrochloride.And use exogenous sodium hydrosulfide(Na HS) and inhibitor of cystathionine-?-synthase(CBS,endogenous H2 S synthetase in the brain) to intervene.24 SD rats were randomly divided into four groups, establishing animal model according to the design of experiment(Saline+Saline group,Saline+morphine group,sodium hydrosulfide+morphine group,hydroxylamine hydrochloride+morphine group).Observing the withdrawal symptoms after finished establishing animal model.And testing the ability of learning and memory with Morris water maze after succeed in establishing animal model.Then,testing the adenylate cyclase(adenylate cyclase, AC), Cyclic Adenosine Monophosphate(Cyclic Adenosine Monophosphate, c AMP) and Protein Kinase A(Protein Kinase, PKA) levels with elisa kit respectively,and detect phosphorylation of cyclic adenosine monophosphate response element binding protein(phosphorylated c AMP response element- binding protein, p-CREB) level using western blot method of rats' hippocampal tissue.Results:(1)Morris water maze result show that:Compared with Con group, learning and memory ability of Mor group and Mor+HA group decreased significantly(P<0.05); ability of Mor+S group increased significantly Compared with Mor group and Mor+HA group(P<0.05).(2)The results of enzyme-linked immune test showed that: Compared with Con group, the level of AC, c AMP, PKA in hippocampus of Mor group and Mor+HA group decreased significantly(P<0.05); the level of AC, c AMP, PKA in hippocampus of Mor+S group increased significantly Compared with Mor group and Mor+HA group(P<0.05);there is no difference between Mor group and Mor+HA group(P>0.05).(3)The p CREB down-expression in morphine addiction rat's hippocampus,lower than Con group(P<0.01); the p CREB up-expression in morphine addiction rat's hippocampus after using exogenous sodium hydrosulfide(Na HS) to intervene,the p CREB expression of Mor+S group higher than Mor group and Mor+HA group significantly(P<0.01). there is no difference between Mor group and Mor+HA group(P>0.05).Conclusion: Long-term-repeatedly use opioids can lead AC–c AMP–PKA– p CREB signal passway down-regulation and the ability of learning and memory to drop; exogenous H2 S may improve learning and memory ability damage due to chronic morphine addiction by up-regulation the AC–c AMP–PKA– p CREB signaling pathway.