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The Effect Of Naloxone On The Aged Rats With Declined-Memory And The Research Of Neurobiological Mechanisms

Posted on:2003-11-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:H XuFull Text:PDF
GTID:1104360062986539Subject:Pathology and pathophysiology
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Opioid and opioid receptor system involve in the process of learning and memory. Endogenous opioid peptides influence the ability of learning and memory through interaction with other transmitter system, hi today, with the prolong of human life-span, the society has payed more attention to senile dementia. Some research indicated that there are some alternations of opioid receptor in Alzheimer's disease and in aged rats. It suggested that opioid receptor involved in the impaired process of learning and memory relative to age. So the decline of learning and memory relative to age may be ameliorated through modulation of opioid system.Naloxone, a classic and non-specific antagonist of opioid receptor has wide spectrum pharmacological action. It can contribute to the modulation of opioid system, enhance the Ach transmitter system function and attenuate the release of superoxide from microglia to elicit neuroprotective action. However, the study on the effect of naloxone on aged rats with declined-memory is very few. And it is well known that estron contribute to the learning andmemory. So the aged female rats were chosen to as the experimental subject in our study. In thisstudy, the performance of Morris water maze were examined after administration with naloxone, firstly. Then the morphysiological alterations of hippocampus were further studied. Alteration of SOD activity of hippocampus and ChAT activity in hippocampus and cortex after treatment with naloxone, and LTP of EPSPs and PS from Schaffer collateral to CA1 region pathway were inspected in order to observe the influence of naloxone on synaptic plasticity. The intention of this research is to discuss the effect of naloxone on age-related memory decline. And the modulation of opioid receptor involved in the declined memory relative to aged subject. This study will supply some evidence to clarify whether nalxone can be used as an agent of modulation of learning and memory in senile dementia.Materials and methodsMaterials1. Animals:6- month- old young and 24-month-old aged Sprague-Dawley (SD) rats. All are female.2. Agents:Naloxone Hydrochloride Injection, Toluidine Blue O. anti-ChAT antibody, SABC kit. SOD kit.3. Apparatus:V C-ll Memory Oscilloscope, MEN-8301 Microelectorde Amplifier, SEN-7203 Electronic Stimulator, SS-201J Isolator, H-300 Transmission Electron Microscope, Visible Light Spectroscopy, HPIAS-1000 Image Analysis System.Methods1. Creation of experimental model:According to the MWM performance of young rats, the aged rats were screened by Morris water maze into two groups, one is aged rats with normal memory, and another is aged rats with declined memory.2. MWM assays:After a month, the all animals were divided into four groups: young group, aged rats with normal memory, aged rats with declined-rats treated with naloxone, and aged rats withdeclined-rats treated with saline as control. The ability of learning and memory were tested by12MWM in a new environment.3. Nissl stain:The animals were divided into three groups: aged rats with normal memory, aged rats with declined-rats treated with naloxone, and aged rats with declined-rats treated with saline as control. Four consecutive slices which is six micron thickness were cut to be stained by Toluidine Blue O.4. The ultrastructurial alteration in CA1 and CA3 region of hippocampus:The animals were divided into three groups: aged rats with normal memory, aged rats with declined-rats treated with naloxone, and aged rats with declined-rats treated with saline as control. Electronic microscope was employed.5. SOD activity of hippocampal tissue assay:The all animals were divided into four groups: young group, aged rats with normal memory, aged rats with declined-rats treated with naloxone, and aged rats with declined-rats treated with saline as control. Visible light spectroscopy was employed.6. Activity of ChAT in paraffin-embedded brain tissue section assay:The animals were divided into two groups: aged rats with decli...
Keywords/Search Tags:Aged rats with declined-memory, Morris water maze, Hippocampus, Superoxide dismutase, Choline acetyltransferase, Long-term potentiation, Naloxone
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