Objective : To establish a laboratory model of heroin addiction in C57BL /6 mice based on associative learning mechanisms． Methods: The black box and white box were selected as the memory training environment， and three behavioral training paradigms were studied : ① Pavlovian conditional position preference ( CPP) training paradigm，mice were placed in the white box for memory reinforcement training for 30 min after intraperitoneal injection of 0. 1 ml of corresponding concentrations (5. 0，10. 0，20. 0 mg / kg) of heroin at 9 :00 a．m．，and 24 h later 0. 1 ml of 0. 9% NaCl solution was injected intraperitoneally into the black box for training，and after the training，the mice were tested for their memory preference for the black and white boxes (movement time of different boxes) . ② A naloxone conditional position aversion ( CPA) training paradigm was conductedbased on the results of the CPP training paradigm. ③ Behavioral sensitization training paradigm，heroin addiction rating scale was established based on the statistical results of 3 behavioral experiments and the lethality of experimental animal disease mice after drug administration．Three different doses of heroin (5. 0，10. 0，20. 0 mg / kg) were selected to induce heroin addiction，and the most appropriate heroin concentration was selected by the results on the rating scale. Results: In the CPP training paradigm，CPP was observed in all heroin groups (P＜0. 05，P＜0. 001，P＜0. 05) ．In the CPA training paradigm，the CPA induction rate was highest in the 10. 0 mg / kg heroin group compared to the control group (P ＜0. 01 ) ．In the behavioral sensitization training paradigm ，all heroin groups caused behavioral sensitization changes (P＜0. 001) ; but the 5. 0 and 10. 0 mg / kg heroin groups did not cause animal mortality．Overall，the 10. 0 mg / kg heroin group had the highest dose score on the rating scale．It could be used as a concentration to establish a stable experimental animal model of heroin addiction． Conclusion The study was effective in establishing a heroin addiction model in mice，and it was suitable for modeling drug concentration screening，with high animal survival rate and simple and practical．The combined learning mechanism can effectively shorten the model establishment period.

Objective: To establish a rat model of preeclampsia (PE) in early pregnancy and to observe the changes in phenotype，pregnancy outcome and cognitive ability of offspring． Methods : The pregnant rats were randomly divided into model group and control group．Ultra-low dose lipopolysaccharide (LPS) (0. 5 μg / kg) and an equal volume of normal saline were injected into the tail vein of pregnant rats on the fifth day of pregnancy．The levels of blood pressure ，12-hour urinary protein ，peripheral blood coagulation factors and placental cytokines in the two groups were measured．Furthermore，placental pathology，pregnancy outcomes，and cognitive abilities of offspring were observed. Results: Blood pressure and urinary protein levels of model group were significantly higher than those of control group levels．Compared with the control group，the levels of platelet and antithrombin Ⅲ (AT Ⅲ) in the peripheral blood of pregnant rats in the model group were lower than those in the control group，while D-dimer was higher than that in the control group，the weight of the fetus and placenta in the model group decreased (P ＜0. 001) ，the expression levels of interleukin ( IL) -6，tumor necrosis factor α ( TNF-α) and interferon gamma (INF-γ) in peripheral blood increased，while the expression level of transforming growth factor β1 (TGF-β1) decreased(P＜0. 001) ．The water maze test showed that the latency of the offspring of the model group to the plat- form was longer than that of the control group (P＜0. 05) ，while the frequency of crossing the platform quadrant and the time of staying in the platform quadrant of the model group were lower than those of the control group (P < 0. 05 ) ．HE and PAS staining showed that there were infiltration of inflammatory cells in the basal layer of placenta， obvious decrease of blood vessels in labyrinthine area，slight edema of renal interstitium and degeneration of local renal tubular epithelial cells in the model group，while there were no above pathological changes in placenta and kidney in the control group． Conclusion A single injection of LPS in early pregnancy can successfully induce PE- related symptoms and adverse pregnancy outcomes such as fetal growth restriction and lead to the decline of cogni- tive ability of offspring.