The Effects Of Nucleus Accumbens PKM ? In Morphine Addiction In Rats

ObjectiveThe roles and mechanisms of nucleus accumbens PKM ? in rats with drug addiction were explored by using molecular biology and behavior methods.The nucleus accumbens was the main brain region we studied,which plays important roles in drug addiction.This study will further clarify the mechanisms of addiction memory,and provide new ideas for effectively intervening,weakening or erasing addictive memory and developing new medical treatment for addiction relapse.Methods(1)The rat model of morphine addiction was prepared by conditioned place preference system and none-tendentiously training program.The open field test was used to examine the exploration of rats.(2)The expression of nucleus accumbens PKM ? was detected by the method of Western blot.(3)Stereotaxic surgeries were performed for micro-injection in the NAc.CPP score was examined after micro-injection of PKM ? inhibitor Zip(0.5?M,5?l each side)into the NAc to explore the effects of ZIP on the extinction and reinstatement of morphine addiction.(4)The expression of acetylized histone H3 was compared by Western blot.To clarify the relationship of histone acetylation and PKM ? expression,the quantity of slice NAc PKM ? from the morphine addictive rats was analyzed after the perfusion of HDAC inhibitor TSA(80?M)for 30 min.Results(1)Morphine induced condition place preference was observed after 5 day's intraperitoneal injection of morphine in rats(p<0.05).(2)The morphinistic rats had less explotatory behavior in the open field test(p<0.05).(3)The expression of nucleus accumbens PKM ? and p-PKM ? significantly increased in morphinistic rats when compared to controls(p<0.05).(4)Micro-injection of PKM ? inhibitor ZIP into the nucleus accumbens accelerated the extinction of morphine-induced CPP(p<0.05).(5)Micro-injection of PKM ? inhibitor ZIP into the nucleus accumbens inhibited the reinstatement of morphine-induced CPP(p<0.05).(6)The expression of nucleus accumbens acH3 significantly increased in morphinistic rats when compared to controls(p<0.05).(7)Western blot results showed that the expression of slice NAc PKM? of from the morphine addictive rats increased after the perfusion of HDAC inhibitor TSA.Conclusion This study indicates that the nucleus accumbens PKM ? plays an important role in morphine addiction.Micro-injection of PKM ? inhibitor ZIP into nucleus accumbens accelerates the extinction and inhibits the reinstatement of morphine-induced conditioned place preference.Furthermore,the increase of NAc PKM ? in morphinistic rats is possibly related with the enhancement of the acetylation of histone H3.