The Effects Of Enriched Environment During Rat Adolescence And Methamphetamine Self-administration On Wnt Signal Pathway

ObjectiveExplore the effect of enriched environment during rat adolescence on the expression of β-catenin and the neuronal activity factor(c-Fos), meanwhile based on the methamphetamine of self-administration model and acute and chronic methamphetamine administration, detecting the expression level of Wnt signal protein and DRD2..MethodsIn Experiment 1, There were additional four groups of animals(IE40, IE30+EE10, IE20+EE20, EE40) were reared from PD 21 to 60. Morris Water Maze test was subsequently carried out and rats were decapitated 2 h later, the expression of β-catenin and c-Fos were detected in the CPu, Hip, NAc, PFC, and VTA brain area. In Experimental 2, METH self-administration performance(acquisition, maintenance, extinction, and reinstatement) was made, then theβ-catenin and DRD2 expression level were tested. In Experiment 3, acute and chronic methamphetamine was executed(i.p.), and the expression of β-catenin and DRD2 were also detected.Result:1. Effects of adolescent enriched environment on Morris Water Maze, β-catenin and c-Fos expression.The present study demonstrated that IE animals spend longer time than EE animals to find the platform, and the group of IE20+EE20 rats were spend shorter time than the group of IE30+EE10 rats to find the platform on the second and third day of the test.Regarding to theβ-catenin expression in the area(PFC, CPu, NAC, VTA, Hip) of rat brain, we find that in Hip the expression of β-catenin level in EE group rats is higher than the IE group rats. The positive expression level of c-Fos(factor of neuronal activity) in NAc、VTA and Hip shows that the EE group rats is higher than the IE group rats, and the c-Fos expression level in group of IE20+EE20 rats is higher than the group of IE30+EE10 rats in Hip.2. The effects on the expression of DRD2 andβ-catenin in methamphetamine self-administrationAfter the maintenance of METH self-administration, the DRD2 expression level in NAc, Hip is higher than the sham group rats. However β-catenin expression in NAc, Hip area is lower than the sham group rat. For the reconstruction of testing, the clue-induced reconstruction rats the expression of β-catenin is higher than the control group rats in PFC, CPu and Hip; the drug-induced reconstruction rats the expression of β-catenin is higher than the control group rats in the five brain area.3. The effects on the expression of DRD2 andβ-catenin in acute and chronic methamphetamineIn the acute methamphetamine administration experiment, the expression of DRD2 in PFC is higher than the saline group rats, and the β-cateninin expression in VTA, Hip, CPu is also higher than the control group rats. However, in the chronic methamphetamine administration, theβ-cateninin expression level in NAc, Hip, CPu is lower than the control rats, and the DRD2 expression level is higher than the control rats in NAc and Hip.Conclusion: Adolescent enriched environment can effectively improve rat’s spatial cognitive ability, as well as the expression of β-catenin and the neuronal activity; the methamphetamine self-administration rats also show higher expression of β-catenin level than control group rats, however the DRD2 expression level show lower than control group rats; in acute and chronic methamphetamine administration experiment; long time methamphetamine passive administration resulted in the inhibition of Wnt/β-catenin, but the expression of DRD2 shows higher in certain brain area.