| Objective To observe the effects of coiydalis yanhusuo and L-tetrahydropalmatine (l-THP) on conditioned place preference (CPP) extinction, various measurements were detected involving glutamic acid (Glu) and NR2B in VTA-NAc-PFC circuit in morphine dependent rats. The corresponding models were exploited based on anti-opioid effects of behavioral, neurotransmitters and receptor administrated to corydalis yanhusuo and l-THP.Methods (1) Effects of CPP were compared with Coiydalis yanhusuo and l-THP.80qualified male SD rats were randomly divided into8groups, NS control group, model group, three dosages of Coiydalis yanhusuo and l-THP. The rats were trained in black and white compartments (the white compartment was drug-paired compartment) after hypodermically injected with morphine and NS for10days (from10mg·kg-1to100mg·kg-1). Different doses (2g·kg-1,1g·kg-1and0.5g·kg-1) of Coiydalis yanhusuo (pure l-THP:0.153mg·kg-1,0.077mg·kg-1and0.038mg·kg-1) were applied to treated with the individuals for21days when the model of CPP was validated on48hours after last training, compared with another group treated with l-THP (3.76mg·kg-1,1.88mg·kg-1and0.94mg·kg-1). The extinction time of each group was recorded every three days (from6-day to21-day). Compared with the extinction time of morphine dependent group48hours after last training, the CPP effect was inhibited if other groups have significant differences for3days.(2) Comparisons of expression of Glu and NR2B in VTA-NAc-PFC circuit on CPP of morphine dependent rats subjected to Corydalis yanhusuo and l-THP.144male SD rats were randomly divided into9groups (n=16) such as NS control group, NS treatment group, model group, three dosages of Corydalis yanhusuo and l-THP. The model of CPP was validated, as described above. when the model of CPP was validated on48hours after last training, the rats of NS control group and model group were harvested for experimental materials. Different doses (2g·kg-1,1g·kg-1and0.5g·kg-1) of Corydalis yanhusuo (pure l-THP:0.153mg·kg-1,0.077mg·kg-1and0.038mg·kg-1) were applied to treated with the individuals for6days after the model of CPP was validated, compared with another group with l-THP (3.76mg·kg-1,1.88mg·kg-1and0.94mg·kg-1) and NS treatment group. Thus, the validations of CPP in those psychological dependence rats, the colorimetry and the immunohistochemistry were applied to detect the content of glutamic acid and the expression levels of NR2B in VTA, NAc and PFC.Results (1) Compared with NS treatment group, the prolonged detention time in drug-paired compartment of model group was observed. Moreover, the reduction effects on CPP were observed in the groups of both Corydalis yanhusuo (2g·kg-1and1g·kg-1) and l-THP (3.76mg·kg-1and1.88mg·kg-1) subjected to medicine for6days. However, the similar effects were found among the model group, Corydalis yanhusuo group (0.5g·kg-1) and l-THP (0.94mg·kg-1) group after21-day treatments (P<0.01, P<0.05).(2) Compared with the NS control group, higher values were detected in fields of VTA, NAc and PFC in model group, involved of both the contents of Glu and the expression levels of NR2B. Compared with the NS treatment group and the model group, the time of animals treated with Corydalis yanhusuo (2g·kg-1and1g·kg-1) and l-THP (3.76mg·kg-1and1.88mg·kg-1) staying in drug-paired compartment was significantly reduced. Moreover, lower values including in the contents of Glu and the expression levels of NR2B were detected in fields of VTA, NAc and PFC in those individuals (P<0.01, P<0.05).Conclusions (1) Corydalis yanhusuo could substantially inhibit morphine induced CPP effects by down-regulated levels of Glu and NR2B in VTA, NAc and PFC.(2) Coiydalis yanhusuo could be play24-fold roles in efficacy of l-THP. The similar effects were observed between the drugs and levels of Glu and NR2B in VTA-NAc-PFC circuit of morphine dependent rats involved in CPP. |
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