Quantitative regional cerebral blood flow MRI of animal model of attention-deficit/hyperactivity disorder

The spontaneously hypertensive rat (SHR) has been widely used as an animal model for attention - deficit/hyperactivity disorder (AD/HD), a developmental disorder that affects 3-5% of school-age children. Quantitative high-resolution (180 x 180 x 1500 pm) perfusion magnetic resonance imaging was performed to evaluate regional CBF in AD/HD rats (SHR, n = 7) and control Wistar Kyoto rats (WKY, n=9) in the frontal cortex, motor cortex, sensory cortex, corpus callosum, hippocampus, thalamus, globus pallidus, caudoputamen and whole brain. The accuracy of repeated cerebral blood flow (CBF) measurements within animals in these brain regions ranged from 3% to 10% (7 repeated measures) and across animals ranged from 15% to 18% (n=7 rats), respectively, indicating highly accurate and reproducible CBF measurements. Regional CBF of the SHR were statistically different from those of the WKY rats in all structures analyzed (P<0.05) except for the caudate putamen (P=0.09) and the globus pallidus (P=0.12). Whole brain CBF of the SHR (1.5 +/- 0.2 ml/g/min, mean +/- S.D.) was similar to 25% higher than that of the WKY rats (1.2 +/- 0.2 ml/g/min), likely due to the hypertensive nature of the AD/HD rat model. Following normalization to eliminate global CBF differences, CBF in the medial prefrontal cortex, a structure thought to be the equivalent of the human dorsolateral prefrontal cortex and widely implicated in AD/HD, was found to be higher in SHR compared to WKY rats (P<0.05). The only other structure that was found to be statistically different after normalization is the corpus callosum (P<0.05). Since resting cerebral blood flow is intricately coupled to resting neural activity, these results suggest that there was abnormal resting neural activity in the medial prefrontal cortex and the corpus callosum between the control and AD/HD animals, consistent with the hyperactivity, impulsivity, inattention, and other AD/HD-like behaviors in this animal model. (c) 2007 Elsevier B.V. All rights reserved.