| Opium dependence and addiction is a very important clinical issue while drug abuse has been a serious social problem. Doctors can effectively release the physiological dependence of drug addicts. However, the high rate of relapse is universally recognized as a tough problem because the control of psychological dependence is not easy . Opiate reinforce effect (such as morphine), which is mediated by dopamine dependent or dopamine independent pathways that converge to nucleus accumbens, play an important role in circle of addiction. It is evidenced that nucleus accumbens is at the main stage of the drug seeking behavioral. Latest research also find that there are morphology, neurochemistry and electrophysiology difference within the subterritory of accumbens-core and shell. But, the role of shell and core in reinforcement is unclear. In present study, rats and rhesus monkey place preference model was used. By stereotaxic lesioning accumbens shell or core, we analyzed the changes in psychological dependence induced by destroying distinct subterritories of accumbens and its characters. So we can establish a basis for understanding the mechanism of addiction, so as to explore the surgical method for drug addition.Results1. Within the 7d discipline rats began to develop preference from 3d and this trend was seriously strengthened during the next 4 days and saturated in 5-th or 6-th day. The longest preference time was about 650s.2. Within the 7d discipline rhesus monkey began to develop preference from 4-th day and this trend was steadily strengthened during the rest of the experiment time and even after the drug administration. There was a significant difference in mean time of preference between 5-th or 6-th day of experiment and pre-experiment. Preference saturated in 10-th day and the longest preference time was about 700s.3. After operation, rats within the core lesion group stayed in the drug box for435s and stayed in the no-drug box for 452s,and significance was not observed. This result suggested ,that the preference of rats with core lesion for drug box was significantly diminished. And the shell lesion group displayed resemble result. So, there is a valid effect on psychological dependence either by lesioning core or by lesioning shell.4. Rhesus monkey within the core lesion group stayed in the drug box for 455s after operation and stayed in the no-drug box for 452s,and significance was not observed. Rhesus monkey within the shell lesion group stayed in the drug box for 466s and stayed in the no-drug box for 442s,and significance was not observed.5. After lesions were establised, all rats showed reduced response to morphine. But, within the relapse procedure under morphine reinforcement, shell group and sham group re-acquired CPP similar to their pre-lesion performance. However, rats with lesions of the NAcc core, but not shell, were severely impaired in the acquisition of morphine-seeking behavior.6. Rhesus monkey, given direct current lesions in either the NAcc core or shell, showed decreased response to morphine. And when recovery was gained monkeys were assessed for their regain of CPP under morphine reinforcement. Shell group re-acquired CPP since the second day of regain procedure and saturased in the 7-th day. However, monkey with lesions of the NAcc core, but not shell, were severely impaired in the acquisition of morphine-seeking behavior. There is significant difference between core and shell lesion group.Conclusions1. Small dosage injection of morphine can induce psychological dependence in rats and rhesus monkeys.2. Rats and monkeys showed parallel CPP behavior, the mean prefer time is 700s.3. Either lesion of core or shell can reduce CPP.4. Only lesion of the NAcc core, but not shell, can reduce the re-acquisition of morphine-seeking behavior.5. Comparable effects of nucleus accumbens on drug addiction exists in different species.6. Nucleus accumbens core may be the neurological basis of reinforce effect of drug addiction. |
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