N-methyl-d-aspartate receptor dysfunction in the prefrontal cortex of stroke-prone spontaneously hypertensive rat/Ezo as a rat model of attention deficit/hyperactivity disorder.

Aim: We previously reported that stroke-prone spontaneously hypertensive rat/Ezo (SHRSP/Ezo) has high validity as an attention deficit/hyperactivity disorder (AD/HD) animal model, based on its behavioral phenotypes, such as inattention, hyperactivity, and impulsivity. Fronto-cortical dysfunction is implicated in the pathogenesis of AD/HD. In this study, we investigated prefrontal cortex (PFC) function in SHRSP/Ezo rats by electrophysiological methods and radioreceptor assay.

Methods: We recorded excitatory postsynaptic potential in layer V pyramidal neurons in the PFC by intracellular recording method to assess synaptic plasticity in the form of long-term potentiation (LTP). We also performed N-methyl-d-aspartate acid (NMDA) receptor binding assay in the PFC and hippocampus using radiolabeled NMDA receptor antagonist [ H]MK-801.

Results: Theta-burst stimulation induced LTP in the PFC of genetic control, WKY/Ezo, whereas failed to induce LTP in that of SHRSP/Ezo. The K value of [ H]MK-801 binding for NMDA receptors in the PFC of SHRSP/Ezo was higher than in the WKY/Ezo. Neither the B nor K of [ H]MK-801 binding in the SHRSP/Ezo hippocampus was significantly different to WKY/Ezo.

Conclusion: These results suggest that the AD/HD animal model SHRSP/Ezo has NMDA receptor dysfunction in the PFC.