Objective: To investigate the effects of Anshen Dingzhiling (ADL) compound on signaling pathways of cyclin-dependent kinase 5(CDK5)/dopamine and adenosine 3'

5'-monophosphate-regulated phospho-protein

32 kDa (DARPP-32)/protein phosphatase 1(PP1) in striatum and prefrontal cortex of spontaneously hypertensive rats (SHR) with attention deficit hyperactivity disorder (ADHD). Method: The 10 Wistar Kyoto rats were used as normal group. 50 SHR rats were randomly divided into model group

methylphenidate (MPH) group (2 mg · kg-1by gavage)

and ADL low

middle

and high dose groups (6.7

13.4

26.7 g · kg-1 respectively)

n=10 in each group. The rats in various groups received corresponding drugs by ig administration

bid. The brain tissues of the rats were taken after 4 weeks of treatment. Real-time PCR

Western blot and immunohistochemistry were used to detect the protein and mRNA expression levels of CDK5

p35

DARPP32

PP1 and cAMP response element binding protein (CREB) in striatum and prefrontal cortex of SHR rats. Result: As compared with normal group

the protein and mRNA expression levels of CDK5

p35 and CREB in striatum and prefrontal cortex were significantly reduced in rats of model group (P<0.05

P<0.01)

the expression levels of DARPP32 and PP1 were significantly increased (P<0.05

P<0.01). After treatment

the protein and mRNA expression levels of CDK5

p35 and CREB in striatum and prefrontal cortex were significantly increased in rats of MPG group and ADL groups as compared with the model group (P<0.05

P<0.01)

while the expression levels of DARPP32 and PP1 were significantly reduced (P<0.05

P<0.01). Conclusion: The acts of SHR rats may be associated with the signaling pathway of CDK5/DARPP32/PP1.ADL can exert the therapeutic action by regulating the signaling pathway of CDK5/DARPP32/PP1.