A Modified Model Of Relapse Of Morphine Related To Psychical Dependence Based On Conditioned Place Preference In Mice

A Modified Model of Relapse of Morphine Related to Psychical Dependence Based on Conditioned Place Preference in MiceCandidate:EU Qiu-shengSupervisor:HUANG MaoInstitution:College of Pharmacy, Second Military Medical University, Shanghai 200433With the development of globalization in economy and regional peace, and the progressing improvement of living standard and the variation of life style since 1980's, drugs abuse has overrun around the whole world, giving rise to more and more serious social and medical issues. Then the prohibition of illegal traffic, of preparing and of selling drugs, and therapy to addiction would be becoming a hot issue. The study of mechanism on drug dependence and new medication to detoxification are flourishing. Up to now, the principal accomplishment in managing of the physical dependence have been achieved, however, people have not found out the mystery of psychical dependence, being incapable of preventing relapse. Moreover, there is not a model of relapse of psychical dependence acknowledged by the public at present. Our study aimed at establishment of new model of relapse of morphine (Mor) related to psychical dependence based on conditioned place preference (CPP) in mice, affording facility to other scholars. Contemporary, we have investigated the effect of total Ervatamia yunnansis alkaloids (TEYA) on blockade of reinstatement of CPP in relapse model and the changes of monoamine transmitters in brains of mice. The major results were described as follows:Part 1. Establishment of model of "relapse"of morphine related to psychical dependence in mice1 Effect of glucocorticoids on faded CPP induced by chronic morphine (Mor CPP)1.1Effect of four doses of hydrocortisone (Hyd) on faded Mor CPPAfter treated with Mor in the dose of 4mgkg? sc , for 7d, the psychical dependence onMor come into being in Inice, the CPP tO the MO side of the twO boxes (White box) aPpeared.From then on, the CPP faded gradualy' and at d9 (ds haing), the mice reSUIned therquOndam habits of biasing the black box. At dl8 ds established CPP, 4 dOses of Hyd,20mg.kg', l0mg'kg', 5mg.kg', 2.5mg.kg-' wer SUbeUtanously bostere to mice. Thecontrol Inice (treated with saline in a period of 7d) were adIninistered with Hyd in the dose of20mg.kg', the tim in blaCk box were ObserVed and recorded ther l5min. ExcePt the ndceof 2.5mg.kg' grouP, all ndce Prefeed tO the white sthe again. And ther was no differenCebetWen grOUs. At d27, the test was ~ and the results wer sndlar tO tha of the bohme. In the contrOl grOU, there was no change ds treatInen with Hyd.l.2 Effect of four doses ofdexamethasone (Dex) on ch MO CPPThe disWd MOr CPP was reinstated in twO grOuPs of ndce ther treated with Dex(2.5mg.kg' and 20Ing.kg" Wvely), and these tWo gnuPs dkl no differ tO eaCh otherBut insignifican resul was ObServed in the other grOuPs. The anlinais ofcOntrl grOuP weregiven Dex in dose of 20mg.kg', no change could be observd.2 ReinstaW effeCt of forCed swinnning in cold water on bo Mor CPP2.l ReinstateInent effeC of fOrced swhain on faded MOr CPP in l5'C wateThe anhals wer forCed to wh in l5'C watr fOr l0min. After 70min, all of themreactiVate, and prefermd the white box again, differing with tha of the contrOl ewuP.2.2 ReinStatement effect of fOrCed swiInrnin on faded MOr CPP in 4C waterThe edmais cOuld Ouly SUStaln fOr han, or they would not survive. the 70min, all ofthem reactiVated, and Prebod the white box again, differing with tha of the contrl pouPanu bo in l5c water3 Effect of three low doses of Mor on faded Mor CPPAt d60 ds treated wt MoL W W ofmce were injeCted MO in three dOses of0.4mg.kg', 0.2mg.kg' or 0.lmg.kg', reSPeCtively The tWo fOrmers gave ou POsitiveresPonses, no significan diWe was fOund betwen them. Whereas the latter has nopositive result, differing with the tWO counterpartS.4 ReinStatemnt effeCt of foot-shOck in ndce on faded Mor CPPThe mice were gbo fOotshOC. Tha of Mor grOuP re-edsbited bias tO white s...