| Objective: The purpose of this study was to explore the level of corticosterone,CORT) and expression of glucocorticoid receptor(GR) in different brain regions of spontaneously hypertensive rat(SHR), which is the model of attention deficit hyperactivity disorder(ADHD), and observe the influence of the classic drug for treatment of ADHD, Methylphenidate, on the SHR’s behavior and the expression level of CORT/GR, for having a further discussion about the relationship between the expression level of CORT/GR in different brain regions and behavior in SHR,and then reveal the function of the CORT/GR expression levels in attention maintenance.Method: The study objects were male SHR and WKY rats postnatal day 21(P21) randomly divided into MPH group and control group, each group have 20 rats. The MPH group rats were administrated MPH 4mg/kg.d, and the control group rats were given the same volume of sterile water twice a day, continuously for 14 days. Before and after the drugs intervention, the cerebrospinal fluid from hippocampus and prefrontal cortex was collected by brain microdialysis, and serum was collected from orbital vein. The CORT of CSF was tested by high performance liquid chromatography, while the serum CORT was tested by immunohistochemical analysis.Then having the open-field testing and LAT maze of the two groups to evaluate the hyperactivity and attention behavior of the rats.Result:(1) After intervention with MPH, it was found that the behavior of SHR had improved both in open field test and LAT maze compared with before intervention, while there was no obvious change in WKY rats.(2) Before intervention, in the SHR, the CORT levels of the hippocampus region( 2.35±0.58 ng/ml) was obviously decreased than that of the prefrontal region(2.79±0.56 ng/ml, P=0.018), while in the WKY rats, the difference between the CORT level in hippocampus(3.43±1.83 ng/ml) and in the prefrontal area(3.31±1.16 ng/ml), show no significant statistically(P>0.05). The CORT level in the hippocampus region of SHR(2.35 ± 0.58ng/ml) was obviously decreased than that of WKY rats(3.43±1.83 ng/ml, P=0.017). After intervention with MPH, it was found that in the hippocampus of SHR group, the CORT level(6.60 ±2.97 ng/ml) had obviously increased compared with before intervention(P= 0.002), while in the prefrontal area of SHR group, compare the CORT levels between before and after intervention,the difference was not significant statistically(P= 0.09).3 Before intervention, the serum CORT of SHR(8.17± 5.20 ng/ml) was obviously decreased than the WKY rats(11.36 ± 6.25 ng/ml,P= 0.015), After intervention with MPH,the serum CORT levels of hippocampus(16.35 ± 6.27 ng/ml) and prefrontal region(15.66 ± 8.30 ng/ml) in SHR group had both increased compared to pre-intervention levels( P= 0.000).(4) Before intervention, the GR expression levels in hippocampus region of SHR(73.58 ± 16.86) was obviously lower than that in WKY rats(111.61 ± 32.46), while in the prefrontal region, the difference was not significant statistically(P>0.05). After MPH administration, the GR expression levesl in SHR hippocampus region(160.60± 77.06, P=0.003) and prefrontal area(157.84 ± 41.90, P=0.035) were obviously increased. The GR expression level in the prefrontal region of WKY rats(183.19±31.63) was increased than control group(109.81±41.64, P=0.000).(5) Correlation analysis showed that the CORT levels of serum and hippocampus region and GR expression in hippocampus region have an negatively correlated with behavioral performance in SHR,and the multiple stepwise regression analysis indicated that the lower serum CORT levels, the more obvious of the core symptoms of ADHD about SHR, while the linear regression analysis suggested that the higher levels of CORT in hippocampus, the higher levlves of serum CORT and GR expression in SHR.Conclusion:(1) SHR exist an obviously decreased of the serum CORT and hippocampus CORT/GR expression levels, suggesting the SHR have dysfunctional of HPA axis.(2) The lower level of serum CORT and hippocampus CORT/GR expression in SHR is closely connected to the ADHD symptoms. MPH can increase the expression of CORT/GR in hippocampus and the level of serum CORT, which are related to the improvement of attention deficit, hyperactivity, which imply that HPA axis is associated with ADHD.(3) The lower GR expression may be an important factor involving the low activity of HPA axis in ADHD model. |
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