| Objective: Choosing the SHR as the attention deficit hyperactivity disorder(ADHD) model. Researching the changes in behaviors, dopamine and noradrenaline, dopamine receptor transpotrers levels in different brain regions by glucocorticoid receptor agonist dexamethaone and glucocorticoid inhibitor RU486. To fing the possible mechanism in ADHD by glucocorticoid receptors(GR)function.Method:(1) Animal grouping and drug intervention: 30 3-week-old(P21) male SHR as the experimental group, and 30 3-week-old(P21) male WKY rats as the control group, each randomly divided into three group of 10 each- GR agonist(DEX group), GR inhibitor(RU486 group) and control group(CON group). GR agonist, GR inhibitors and control rats rats were administered DEX 0.5mg/kg.d, RU686 54mg/kg.d, saline 0.5ml/kg.d by intraperitoneal injection at 8:00am, for 14 consecutive days.(2) Behavior evaluation: open field and Y maze before and after the pharmacological interventions to evaluate spontaneous motor activity and attention.(3) The levels of dopamine, norepinephrine in rat brain: The micro-dialysis machine was used to get extracellular fluid in different brain areas(prefrontal area, striatum region) which was detected dopamine, norepinephrine concentration by high performance liquid chromatography detection.(4) Dopamine transporter(DAT) expression: By using immunohistochemistry method DAT expression was detected in brain areas(prefrontal region, striatum area).Results:(1) In open field test:In SHR groups, the frequency of crossing the grid and upright were significantly reduced in DEX group( t=2.75, P=0.023;t=6.36, P< 0.001). In RU486 group, there was no significant changes in CON group(P>0.05).(2) In Y maze test : The correct responses were significantly higher in DEX group in SHR group( t=4.38, P=0.002) and in WKY group(t=16.29, P<0.001), but there were no significant change in RU486 group and CON group(P>0.05). Meanwhile, DEX group in SHR and WKY rats had significantly higher correct response rate than RU486 group and CON group(SHR group: F= 73.85, P<0.001; WKY group: F=17.60, P<0.001), while there was no significant between RU486 and CON group difference(P > 0.05).(3) The levels of DA, NE in brain: Compare with before intervention, DA content in the frontal region of SHR was increasing in DEX group(t =10.68, P<0.001), RU486 group were lower(t=2.48, P=0.035). There was no significant difference in CON group(t=0.69, P=0.509); NE content showed no significant changes in each group(DEX group: t=0.95, P=0.367; RU486 group: t=1.74, P= 0.116; CON group: t=0.27, P=0.791). In the caudate nucleus of SHR. DA content was increased in DEX group(t=4.81 P=0.001), lower in RU486 group(t=14.06, P<0.001), no changes in CON group(t=0.76, P=0.469); NE content was increased in DEX group(t=4.01, P=0.003), lower in RU486 group(t=8.70, P<0.001) and no significant change in CON group(t=1.41, P=0.171). DA content was no significant change in prefrontal area of WKY rats(DEX group: t=0.42, P=0.684; RU486 group: t=0.19, P=0.885; CON group: t=0.69, P= 508). NE content had no significant change(DEX group: t=0.273, P=0.79; RU486 group: t=0.95, P=0.367; CON group: t=1.74, P=0.116). In WKY caudate nucleus, DA content was increased in DEX group(t=15.14, P<0.001), lower in RU486 group(t=10.58, P<0.001), no significant changes in CON group(t =1.47, P=0.176). NE content in DEX group, RU486 group and CON group had not significant change(DEX group: t = 0.53, P=0.611; RU486 group: t=1.43, P=0.187; CON group: t=0.73, P=0.485).(4) Immunohistochemistry of DAT: In SHR prefrontal area, the expression of DAT in DEX group was significantly less than in the RU486 and CON groups(F=25.95, P<0.001). In the striatum area of SHR, DAT expression in DEX group was significantly lower than that in RU486 group and CON group(F=35.373, P<0.001).In the prefrontal area of WKY rats, DAT expression in each group had no significant difference(F=0.35, P=0.708). In WKY rat striatum area, DAT expression had no significant difference in each group(F=0.59, P>0.05). In WKY rat prefrontal area, DAT expression in each group was lower than SHR group(DEX group: t=2.79, P= 0.012; RU486 group: t=8.70, P<0.001, CON group: t=10.19, P<0.001). DAT expression in WKY rat the striatum area was generally lower than SHR group(DEX group: t=9.60, P<0.001, RU 486 group: t= 3.76, P<0.001, CON group: t=19.36, P<0.001).Conclusion: GR agonists can reduce the expression of DAT and increase DA, NE levels in prefrontal area and striatum area, to relieve hyperactivity and attention deficit in SHR.The effect of GR Function on dopaminergic neurotransmitter may be involved in the pathogenesis of ADHD. |
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