Attention deficit/ hyperactivity disorder (AD/HD) is a mild developmental disorder (DSM-5). We reported that stroke-prone spontaneously hypertensive rat/Ezo (SHRSP/Ezo) had high validity as an AD/HD animal model, because of its behavioral phenotype. Recently, we revealed the NMDA receptor dysfunction on excitatory synapse in the prefrontal cortex (PFC) of SHRSP/Ezo. D-serine, an endogenous co-ligand for NMDA receptor, is one of new drug targets for the treatment of several psychiatric disorders. D-serine is biosynthesized from the optical conversion of L- to D- by serine racemase (SR), and metabolized by D-amino acid oxidase (DAAO). Here, we evaluated the serine kinetics in the PFC of SHRSP/Ezo and assessed the effect of DAAO inhibitor on AD/HD-like behaviors of SHRSP/Ezo.
At 6 weeks old, SHRSP/Ezo and its genetic control, WKY/Ezo were anesthetized and immediately decapitated. The PFC tissue was trimmed on ice for analysis of SR and DAAO expression by western blotting and measurement of serine concentration by HPLC-ECD system. Moreover, we performed local injection of DAAO inhibitor (5 microgram/side) into the PFC and assessed AD/HD-like behaviors using Y-maze test.
DAAO in the PFC of SHRSP/Ezo was significantly higher expression compared with WKY/Ezo, although SR was not significant. Correspondingly, D-/L- ratio of serine in the PFC of SHRSP/Ezo was lower than that of WKY/Ezo. Furthermore, local injection of DAAO inhibitor into the PFC improved inattention and hyperactivity of SHRSP/Ezo. These results suggest that DAAO inhibitor can be a possible candidate for treatment of AD/HD.
