[P3-15] Glucocorticoids/Glucocorticoid Receptors Effects on Dopaminergic Neurotransmitters in ADHD Rats
Objective: To investigated the effect and the underlying mechanize of Glucocorticoids/ Glucocorticoid receptors (GCs/GR) on dopaminergic system in ADHD.
Method: 30 WKY male rats and 30 SHR male rats were evently divided into 3 groups randomly as follows: GR agonist group (DEX), GR inhibitor group (RU486 ) and control group (CON). Open field test and Y maze were performed before and after drug administrated to assay rats behavior, and the level of dopamine, norepinephrine and dopamine transporter (DAT) in the prefrontal cortex and striatum were tested by HPLC.
Results: In behavior test, the ADHD symptoms were improved after DEX treatment in both SHR and WKY rats (P<0.01). In SHR rats, the level of DA in the prefrontal cortex and striatum increased in DEX group (P < 0.001), but decreased in RU486 group (P < 0.05). NE level in striatum increased in DEX group (P < 0.001), but decreased in RU486 group (P < 0.001) . However, there was no significant difference in CON group (P > 0.05). Immunohistochemistry showed that DAT expression in the prefrontal cortex and striatum of SHR rats was obviously less in DEX group than in RU486 and CON group (P < 0.001).
Conclusion: By regulation of glucocorticoid receptor, GR agonist can decrease DAT expression, which resulting in the increasing of DA and NE level in brain and ameliorate ADHD symptoms. It is suggested that the GR function in the central nervous system may be involved in the pathogenesis of ADHD.
Acknowledgements
Supported by the grant from National Natural Science Funds of China (81371262)
Method: 30 WKY male rats and 30 SHR male rats were evently divided into 3 groups randomly as follows: GR agonist group (DEX), GR inhibitor group (RU486 ) and control group (CON). Open field test and Y maze were performed before and after drug administrated to assay rats behavior, and the level of dopamine, norepinephrine and dopamine transporter (DAT) in the prefrontal cortex and striatum were tested by HPLC.
Results: In behavior test, the ADHD symptoms were improved after DEX treatment in both SHR and WKY rats (P<0.01). In SHR rats, the level of DA in the prefrontal cortex and striatum increased in DEX group (P < 0.001), but decreased in RU486 group (P < 0.05). NE level in striatum increased in DEX group (P < 0.001), but decreased in RU486 group (P < 0.001) . However, there was no significant difference in CON group (P > 0.05). Immunohistochemistry showed that DAT expression in the prefrontal cortex and striatum of SHR rats was obviously less in DEX group than in RU486 and CON group (P < 0.001).
Conclusion: By regulation of glucocorticoid receptor, GR agonist can decrease DAT expression, which resulting in the increasing of DA and NE level in brain and ameliorate ADHD symptoms. It is suggested that the GR function in the central nervous system may be involved in the pathogenesis of ADHD.
Acknowledgements
Supported by the grant from National Natural Science Funds of China (81371262)