Accumbal Dopamine And DOPAC Activity On Conditioned Place Aversion Rats

ObjectiveTo determinate the concentration of Dopamine and3,4dihydroxyphenylacetic acid in the shell of accumens nucleus on Chronic morphine dependence rats during Conditioned Place Aversion (CPA) formation,subsided and reinstatement, so that we could investigate the neural biochemical mechanism of morphine induced negative reinforcement.Methods1.69male Sprage-Dawley rats are randomly divided into experimental group (morphine+naloxone, MN) and control group (morphine+saline, MS; saline+naloxone, SN), after6.5days morphine injection,we use naloxone(0.3mg/kg,IP) for once injection to establish the CPA rat model. During the7th-13th days, CPA rats will receive the subside behavioral training twice per day. On the14th days, subsided CPA behaviors will proceed a reinstatements by drug related cues.2. At the time of3-5days after the guide cannula implantation, the time before and after CPA establishment, the time after CPA subside and reinstatement, extracellular fluid of AcbSh will be collected by microdialysis. We will detect the concentration of DA and DOPAC in the dialysate by HPLC-EC.3. The results are expressed as the mean±SEM,unless specially indicated. Statistical comparison of behavioral measures among groups are conducted by oneway-ANOVA., Behavioral and neurochemical measures within individual groups were compared by Independent sample t-test. Neurochemical measures within a sampling period were first analysed with repeated-measures ANOVA. Differences with a P-value<0.05were considered significant. All statistical analyzes were performed using SPSS16.0. Results1. For six and a half days morphine injection and once naloxone injection (0.3mg/kg IP), we can successfully establish CPA model, experimental rats have showed obvious aversive motivation; After seven days of extinctive training, CPA behaviours can be successfully extincted. However, when exposed to CPA conditions again, CPA behavior could be successfully reinstated.2. The levels dopamine and DOPAC in MN group are significantly increased after the establishment of CPA (P<0.01), however, no significant difference are observed in MS group and SN group (P>0.05). After a week-long extinctive training, dopamine and DOPAC in the shell of CPA rats’ nucleus accumbens are significantly decreasing. At the last time of extinctive training, there has been no significant statistical differences. After reinstatement training, the levels of dopamine and DOPAC of MN group increased significantly (P<0.01).Conclusion1. Low dose of naloxone can result in morphine dependent rats produced CPA. After one-week long behavior training in drug-free state, the CPA behavior can be successfully subsided; However,when exposed to drug-related environment again, the CPA behavior can be reconstructed;2. Dopamine and DOPAC in the shell of accumbens nucleus may participate in the formation of CPA, the dopamine mesolimbic system may play a very important role in the regulation of morphine aversive motivation. To intervene the changes of dopamine may be one of the potential target for clinical treatment of opiate addiction.