Effects of Zishen Xieqing Tang on Dopamine Signaling Pathway of Desensitization/Resensitization in Attention Deficit Hyperactivity Disorder Rats' Prefrontal Cortex

  OBJECTIVE   To investigate the effects of Zishen Xieqing Tang(ZXT)on attention deficit hyperactivity disorder (ADHD) related behavior and dopamine signaling pathway of desensitization and resensitization in spontaneously hypertensive rats' prefrontal cortex.

  METHODS   10 Wistar Kyoto rats were set as normal control group. 50 SHR rats were randomly divided into 5 groups including model group, methylphenidate (MPH) group (2 mg·kg^-1by gavage), and high, middle, low dose of ZXT groups(ig ZXT with the crude drug dosage 6.0, 12.1, 24.1 g·kg^-1 respectively). Rats were orally given the drugs twice a day, then, behavior experiment was done to test the ADHD related behavior changes. After 4 weeks of treatment, the prefrontal cortex of rats were collected for further study. Real-time PCR and Western blot were used to test the protein or mRNA expression of GRK-6, β-arrestin2, NCS-1, PP2A and PSD-95 in SHR rats' prefrontal cortex.

  RESULTS   MPH group and ZXT groups could improve the ADHD related behavioral performance of SHR. Statistic difference of β-arrestin2, GRK-6, NCS-1, PSD-95, PP2A and PKA expression were observed among different groups (P < 0.05). Comparing with normal control group, the β-arrestin2, NCS-1, PSD-95 and PP2A expression of SHR rats' prefrontal cortex in model group were much lower (P < 0.05). After treatment with ZXT, comparing the model group, the expression of β-arrestin2, NCS-1, PSD-95 and PP2A in MPH group and every-dosage group of ZXT were much higher in both parts (P < 0.05). At the meanwhile, the expression of GRK-6 was observed on the contrary behavior.

  CONCLUSION   Both MPH and Zishen Xieqing Tang can affect the function of dopamine receptors by regulating desensitization and re-sensitization, thus improve the ADHD related symptom.