Dissertation
Dissertation > Medicine, health > Neurology and psychiatry > Psychiatry > Mental disorders of toxic > Drug-induced mental disorders

Effects of Exogenous CCK-8on Morphine Induced Impairment of Learning and Memory

Author ZuoGuoQing
Tutor MaChunLing
School Hebei Medical University
Course Forensic
Keywords Exogenous CCK-8 morphine addiction addiction memory step-down test LTP neurotransmitte
CLC R749.61
Type Master's thesis
Year 2014
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Opioid dependence is a chronic relapsing disorder in the brain, which isrelated to adaptive alteration of learning and memory. Cholecystokininoctapeptide (CCK-8) is the most potent endogenous anti-opioid peptide. In ourprevious study, we found that CCK-8treatment alone could improve spatialreference memory and CCK-8before the training or test significantlyimproved impairment of memory acquisition induced by morphine. Thisresearch is aimed to determine the effect of CCK-8on impairment of learningand memory in morphine-treated mice and its mechanism of receptor.1Effect of exogenous CCK-8on impairment of escape response inmorphine-treated miceObjective: This part of study aimed to investigate the effect of exogenousCCK-8on impairment of memory on the single-trial step down inhibitoryavoidance task in morphine induced mice and its mechanism of receptor.Methods: To observe effect of morphine or exogenous CCK-8on theformation, retention and retrieval of memory, morphine was subcutaneousinjected at dose followed10mg/kg or different doses (0.001,0.01,0.1and1μg) of CCK-8were given by lateral ventricle injection. Then, CCK-8wasgiven by lateral ventricle injection15min before morphine injuction in orderto observe the effect of CCK-8on the formation of memory inmorphine-induced memory impairment. Last, CCK-antagonists were givenwith CCK-8by lateral ventricle injection before morphine injuction toinvestigate the role of CCK-antagonist in CCK-8regulation ofmorphine-induced memory formation impairment.Results:①Acute morphine (10mg/kg30min before training, s.c.)treatment impaired the formation of memory, the latency for the animal to stepdown from the platform was shortened, while had no effect on the retention and retrieval of memory after training or before test.②Acute exogenousCCK-8(001,0.01,0.1and1μg, i.c.v) have no effect on the formation, retentionand retrieval of memory before or after training or before test.③exogenousCCK-8(15min before morphine injection) improved the formation ofmemory in morphine-induced memory impairment.④L-365.260(10μg, i.c.v.)were co-administrated with CCK-8(1μg, i.c.v.)15min before morphine (10mg/kg, s.c.) treatment can inhibit the effect of exogenous CCK-8. The effectof CCK-8on morphine-induced memory impairment was related to CCK2receptor.Summary: This study reveals the exogenous CCK-8improved theformation of memory in morphine-induced memory impairment andmodulated the effect of CCK-8on learning and memory through CCK2receptor.2Effects of exogenous CCK-8on morphine induced impairment ofhippocampal long-term potentiationObjective: In the present study, we aimed to determine the exact effectsof exogenous CCK-8at various doses on hippocampal long-term potentiationand the the exact effects of exogenous CCK-8on morphine-inducedimpairment of hippocampal long-term potentiation, then explore themechanism of effects of exogenous CCK-8on morphine induced learning andmemory impairment.Methods: To observe effect of morphine or exogenous CCK-8onhippocampal long-term potentiation, morphine was subcutaneous injected atdose followed30mg/kg or different doses (0.001,0.01,0.1and1ug) ofCCK-8were given by lateral ventricle injection. Then, CCK-8was given bylateral ventricle injection15min before morphine injuction in order to observethe effect of CCK-8on hippocampal LTP in morphine-treated rats. Last, CCK-antagonists were given with CCK-8by lateral ventricle injection beforemorphine injuction to investigate the role of CCK receptor in CCK-8regulation of morphine-induced impairment of hippocampal LTP.Results:①Acute morphine treatment significantly inhibited the hippocampal LTP, and the PS amplitude after HFS decreased significantly.②A significant enhancing effect of CCK-8at1μg and0.1μg on hippocampalLTP was markedly facilitated, but the PS amplitude in the0.001μg and0.01μg CCK-8-treated groups were not changed when compared to the salinegroup. Co-treatment of CCK2receptor antagonists with CCK-8microinjectiondecreased the PS amplitude and significantly reversed the accelerating effectof CCK-8on hippocampal LTP.③The tests revealed a significantimprovement in the effect of1μg CCK-8on morphine-induced hippocampalLTP inhibition, and0.1μg CCK-8pre-treated group showed no significantdifference.④CCK2receptor antagonist (L-365.260) significantly blocked theeffect of CCK-8on hippocampal LTP inhibition when it was co-administratedwith CCK-8, but the effect of CCK1receptor antagonist (L-364.718) did notchange the effect of CCK-8.Summary: The tests revealed a significant improvement in the effect ofCCK-8on morphine-induced hippocampal LTP impairment. CCK2receptorantagonist (L-365.260) significantly blocked the effect of CCK-8. The resultsindicate that exogenous CCK-8significantly improved morphine-inducedhippocampal LTP inhibition and inferred the possible role of the CCK2receptor in this process.Conclusion: Exogenous CCK-8improved the formation of memory inmorphine-induced memory impairment on the single-trial step downinhibitory avoidance task and modulated the effect of CCK-8through CCK2receptor. Otherwise, CCK-8significantly improved the effect of CCK-8onmorphine-induced hippocampal LTP inhibition and CCK2receptor antagonist(L-365.260) significantly blocked the effect of CCK-8. The results indicatethat exogenous CCK-8significantly improved the effect of morphine-inducedmemory and learning impairment through CCK2receptor.

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