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THE EFFECT OF METHYLPHENIDATE HYDROCHLORIDE COMBINED WITH PLATYCLADI SEED EXTRACT ON ATTENTION DEFICIT HYPERACTIVITY DISORDER IN A MURINE MODEL

JINHUA ZHAO ^1,2, JIHONG TANG ^1*, XIAOYAN SHI ¹

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The study aimed to evaluate the therapeutic effect and the underlying mechanism of methylphenidate hydrochloride combined with Platycladi seed extract on attention deficit hyperactivity disorder (ADHD) in a murine model. Forty-eight SPF male SHR rats were divided into 4 groups as follows: a rat model of attention deficit hyperactivity disorder that received 10 mL/kg bw/day saline solution, a methylphenidate hydrochloride group treated with 3.75 mg/kg bw/day methylphenidate hydrochloride, a Platycladi seed extract group treated with 9 mg/kg bw/day Platycladi seed extract, a methylphenidate hydrochloride (MHCRT) combined with Platycladi seed extract group treated with 3.75 mg/kg bw MHCRT plus 9 mg/kg bw/day Platycladi seed extract. Twelve Wistar Kyoto rats were used as a normal group that received 10 mL/kg bw/day saline solution. After 14 days of treatment the combination of MHCRT and Platycladi seed extract significantly reduced the serum NE (norepinephrine) level in rats and significantly increased the DA (dopamine) and 5-HT (serotonin) levels along with improving neurobehavioral changes related with ADHD with a superior effect compared with the use of Platycladi seed extract or MHCRT alone. Regarding the protein expression level in brain tissue when associated to the standard treatment with MHCRT, Platycladi seed extract additively increased the effect of MHCRT and succeeded to significantly increase the expression of GIT1 (ARF GTPaseactivating protein), CDH13 (cadherin 13), BDNF (brain-derived neurotrophic factor), CaM (calmodulin) and NET (adrenergic transporters) and significantly decreased the expression of LPHN3 (latrophilin 3) compared with the model group. In serum, the association of Platycladi seed extract with MHCRT additively increased the effect of MHCRT alone on increasing the protein level of β-EP (betaendorphin), IP3 (inositol triphosphate) and Glu (Glutamine synthetase) and decreased PG (plakoglobin) level compared with the model group. In conclusion, Platycladi seed extract can potentiate the effect of standard MHCRT treatment by regulating the expression of neurotransmitters in an ADHD murine model.