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.

Abstract

AimWe 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.MethodsWe 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 [3H]MK‐801.ResultsTheta‐burst stimulation induced LTP in the PFC of genetic control, WKY/Ezo, whereas failed to induce LTP in that of SHRSP/Ezo. The K d value of [3H]MK‐801 binding for NMDA receptors in the PFC of SHRSP/Ezo was higher than in the WKY/Ezo. Neither the B max nor K d of [3H]MK‐801 binding in the SHRSP/Ezo hippocampus was significantly different to WKY/Ezo.ConclusionThese results suggest that the AD/HD animal model SHRSP/Ezo has NMDA receptor dysfunction in the PFC.