Attention-deficit/hyperactivity disorder (AD/HD) is a type of neurodevelopmental disorder. Many clinical and animal studies have indicated that prefrontal cortex (PFC) dysfunction is involved in AD/HD pathogenesis. Moreover, dopamine reuptake inhibitors and releasers are used clinically for drug treatment of AD/HD. Juvenile stroke-prone spontaneously hypertensive rat/Ezo (SHRSP/Ezo) reportedly have high pharmacological validity as an AD/HD animal model, based on its behavioral phenotypes such as inattention, hyperactivity, and impulsivity. Recently, we revealed that SHRSP/Ezo had N-methyl-d-aspartate acid (NMDA) receptor dysfunction in the PFC. D-serine acts on NMDA receptor glycine binding sites as a co-agonist, and abnormal D-serine levels have been reported in psychiatric disorders. In this study, we evaluated the levels of D-serine in the PFC, and expression of its biosynthesis enzyme serine racemase (SR) and its degradation enzyme D-amino acid oxidase (DAAO) to investigate AD/HD pathogenesis.
In the PFC of SHRSP/Ezo, we found lower D-serine levels and lower serine enantiomers ratios (D-serine/ D-serine + L-serine, DL ratio) compared to genetic control, Wistar Kyoto/Ezo (WKY/Ezo) rat . DAAO expression was increased in the PFC of SHRSP/Ezo. However, SR expression was unaltered between SHRSP/Ezo and WKY/Ezo. Furthermore, AD/HD-like behaviors in SHRSP/Ezo were improved by the microinjection of AS057278, a DAAO inhibitor, into the PFC.