Rotundine Inhibition And Its Neural And Biochemical Mechanisms Of Cocaine Cpp In Rats

Cocaine abuse has become a serious social problem in the world, which is a chronic brain disorder characterized by relapse. There is so far no effective treatment to stop the relapse of drug use after temporal withdrawal. Serious craving (psychic dependence) has been known to be the main reason of drug relapse. It is reported that antagonize D2 receptors in the CNS could inhibit cocaine craving behaviors, including cocaine-induced conditioned place preference (CPP) and self-administration. Work has shown that 1-tetrahydropalmatine (1-THP) could increase the release of endogenous dopamine by antagonizing D2 receptors in the central nerve system. Our previous work has demonstrated that 1-THP has good effect on rat DD, which was induced by MA. It seemed worthwhile to test whether 1-THP would also be effective in suppressing cocaine craving by antagonist D2 receptors. To test this hypothesis, we investigated the effect of 1-THP on the expression of cocaine-induced CPP in the present study. We then explored the brain areas involved in the effect of 1-THP by micro-infusion, into corresponding sites in the rat brain. We also observed the effect of 1-THP on the abundance of phospho-CREB in rat brain. The results are as follows:1. CPP could be induced by repeated i.p. administration of cocaine ( 20 mg/kg ), Once developed, it maintained for at least 13 days under daily testing without cocaine reinforcement, indicating that cocaine has strong potential of being addicted.2. We are the first to identify the suppression of cocaine-induced CPP in rats by 1.25, 2.5, 5 mg/kg 1-THP , but not 0.625 mg/kg 1-THP (P <0. 001), without affecting the natural place preference in rats.3. Micro-infusion of 1-THP into nucleus accumbence and vebtral tegmental area, but not into amygdala, could suppress cocaine-induced CPP. The suppression indicats that the effect of 1-THP is mediated in nucleus accumbence and vebtral. tegmental area in rats.4. CPP could not be induced by repeated i.p. administration of 1-THP ( 1.25 or 5 mg/kg ).5. Repeated administration of cocaine does not significantly reduce the expression of phospho-CREB in nucleus accumbens and basolateral amygdala.6. In cocaine CPP rats, which could be raised significantly by treatment of 10mg/kg 1-THP for one time.In summary, the findings suggest that cocaine-induced CPP expression in the rat can be supressed by 1-THP in a dose dependent manner, i. e. 5mg/kg works and 0. 625 mg/kg does not. The effect 1-THP is mainly in the nucleus accumbens and ventral tegmental area of the limbic brain. This effect of 1-THP is supposed to be mediated by an increase of phospho-CREB in the nucleus accumbens, which might inhibit behaviral sensitization induced by cocaine.