[P3-16] Effects of glucocorticoid receptor function on the central 5-HT system in rats with ADHD
Objective: To investigate the relationship between 5-HT sand corticosterone(CORT) in rat model of ADHD (SHR) and its mechanism in ADHD.
Method:P21 SHR rats were randomly divided into ADHD control group (SHR group), GR agonist group (SHR+DEX group) and GR inhibitor group (SHR+RU486 group), WKY rats were served as the normal control group (WKY group), 15 rats in each group. The rats in GR agonist group, GR inhibitor group and control group were treated dividedly with dexamethasone (0.5 mg/kg.d), mifepristone (54 mg/kg.d), and neutral saline. Open-field test and lat maze were used to measure the ADHD behavior. The extracellular fluid from prefontal cortex was extracted by microdialysis and the level of 5-HT was detected by high performance liquid chromatography. The expression of GR, 5-HT1A and 5-HT2A receptor were investigated by immunohistochemistry.
Results: The results showed that behavior performances in SHR was poorer than in WKY rats (P <0.05), but which was improved in SHR+DEX group(P < 0.05). The levels of 5-HT in the prefrontal cortex: in SHR+DEX group > in SHR group > in SHR+RU486 group and in WKY group(P < 0.05). Immunohistochemistry showed that GR and 5-HT2AR expression in the prefrontal cortex in SHR group < in WKY group (P < 0.05), while the expression of 5-HT1AR was opposite (P < 0.05). The level of GR and 5-HT1AR were negatively correlated (r=-0.490, P=0.026), while GR level was positive correlation with 5-HT2AR (r=0.832, P=0.008).
Conclusion: Increasing expression of 5-HT and 5-HT2AR or decreasing 5-HT1AR may related to improvement of ADHD symptom.
Acknowledgements
Supported by the grant from National Natural Science Funds of China (81371262)
Method:P21 SHR rats were randomly divided into ADHD control group (SHR group), GR agonist group (SHR+DEX group) and GR inhibitor group (SHR+RU486 group), WKY rats were served as the normal control group (WKY group), 15 rats in each group. The rats in GR agonist group, GR inhibitor group and control group were treated dividedly with dexamethasone (0.5 mg/kg.d), mifepristone (54 mg/kg.d), and neutral saline. Open-field test and lat maze were used to measure the ADHD behavior. The extracellular fluid from prefontal cortex was extracted by microdialysis and the level of 5-HT was detected by high performance liquid chromatography. The expression of GR, 5-HT1A and 5-HT2A receptor were investigated by immunohistochemistry.
Results: The results showed that behavior performances in SHR was poorer than in WKY rats (P <0.05), but which was improved in SHR+DEX group(P < 0.05). The levels of 5-HT in the prefrontal cortex: in SHR+DEX group > in SHR group > in SHR+RU486 group and in WKY group(P < 0.05). Immunohistochemistry showed that GR and 5-HT2AR expression in the prefrontal cortex in SHR group < in WKY group (P < 0.05), while the expression of 5-HT1AR was opposite (P < 0.05). The level of GR and 5-HT1AR were negatively correlated (r=-0.490, P=0.026), while GR level was positive correlation with 5-HT2AR (r=0.832, P=0.008).
Conclusion: Increasing expression of 5-HT and 5-HT2AR or decreasing 5-HT1AR may related to improvement of ADHD symptom.
Acknowledgements
Supported by the grant from National Natural Science Funds of China (81371262)