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Morphine Affected Thioredoxin Expression In Mice Brain

Posted on:2010-09-01Degree:MasterType:Thesis
Country:ChinaCandidate:K LiFull Text:PDF
GTID:2154330332478142Subject:Biochemistry and Molecular Biology
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Drug addiction is a brain disease of chronic and relapse. Repeated use of abuse drugs can cause adaptive changes in the central nervous system, such as, tolerance, physical dependence, psychological dependence and other complex pathophysiological process, accompanied by drug-seeking, drug taking and other compulsive behavior. Druggers become querulous, anger, low-self-esteemed, cunning, and they have not responsibility for family and community. Drug addiction is a malignant brain disease, as well as worldwide medical problems now.Several brain areas are involved in drug addiction:the prefrontal cortex, temporal cortex, locus coeruleus, globus pallidus, ventral tegmental area, nucleus accumbens, the amygdala, hippocampus, hypothalamus, caudate nucleus and so on. Opioid drugs such as heroin, morphine, pethidine, methadone, are associated with these brain areas. Drugs activate some signaling pathway through the intecaction of these brain areas. These signaling pathways include:opioid receptor, dopamine pathways, cannabis receptor, glutamate receptor and the mitogen-activated protein kinase pathway. These pathways may mediate neural excitement or inhibition, and alter synaptic plasticity, learning, memory and soon.To clarify its developing and processing mechanisms is important for treating abuse of drugs, it will be benefit for dividuals and the whole community. Therefore, adoption of new research strategies and to explore new therapeutic targets have an important social and scientific significance.A body of evidence showed that drug addiction also may cause redox imbalance. In vivo and in vitro experiments confirmed that heroin could induce significant increase of lipid peroxides. Thioredoxin is a low molecular weight protein and it is ubiquitous in prokaryotic and eukaryotic cells. Thioredoxin provides electrons to target proteins through the disulfide exchange reaction. Thioredoxin is reduced by thioredoxin reductase and NADPH. Thioredoxin system is comprised of thioredoxin, thioredoxin reductase and NADPH, playing multiple biological functions, such as anti-oxidation, anti-apoptosis and promoting cell proliferation. Therefore, research on the relationship between thioredoxin and drug addiction may provide new ideas for treatment of drug addiction.Morphine is the main active component of opium poppy, and it is also an effective opioid analgesic drug. Morphin exerts activity of relieving pain by directly acting on the central nervous system. Morphine has a high risk to develope addiction. It is easy to form physiological and psychological dependence and tolerance. Morphine is one of typical opioid drugs. Study of intracellular signal pathways on morphine addiction is more representative. Our study has demonstrated that morphine can affect thioredoxin expression in SH-SY5Y cells. Now we will detect the expression of thioredoxin in some brain areas of mice after morphine exposure in this study.The results confirmed that a dose of 20 mg/kg of morphine administration for two hours, thioredoxin expression was significantly reduced in mouse cerebral cortex, hippocampus and spinal cord. However, expression of CDK5 and phosphorylation level of CREB or GSK-3βwasn't affected by acute morphine administrationn in mouse cerebral cortex, hippocampus. Conditioned place preference was developed after a total of three times,20 mg/kg every other day of morphine administration, and thioredoxin expression was markedly reduced in mouse cerebral cortex, however, thioredoxin significantly increased in hippocampus. More interestingly, expression of thioredoxin wasn't affected after chronic morphine exposure in mouse spinal cord.
Keywords/Search Tags:thioredoxin, morphine, cerebral cortex, hippocampus, mice
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