Remodeling of neural networks in the anterior forebrain of an animal modelof hyperactivity and attention deficits as monitored by molecular imaging probes

Remodeling of neural networks in the anterior forebrain of an animal model of hyperactivity and attention deficits as monitored by molecular imaging p robes. These studies report on the remodeling of neural networks which are likely to be the consequences of the segmental defect in the anterior foreb rain of an animal model of hyperactivity and attention-deficit, the juvenil e prehypertensive male spontaneously hypertensive rat (SHR). Molecular biol ogy and microscope imaging techniques were used such as: (i) dopamine (DA) D-1 and D-2 receptors by radioligand binding studies; (ii) the Ca2+/Calmodu lin-dependent protein kinase II (CaMKII); (iii) transcription factors (TF) such as c-FOS by Immunocytochemistry; and (iv) the respiratory chain enzyme cytochrome-oxidase (C.O.), as markers of neuronal activity in the anterior forebrain of SHR and Wistar Kyoto normotensive (WKY) controls rats. Microc omputer-assisted high-resolution image analysis using DA receptor binding a nd C.O., as probes revealed by cross-correlations among different regions w ithin brain an altered cross-talk in the anterior forebrain of the SHR as c ompared to the controls. In particular, an altered cross-talk was also obse rved within the amygdala complex in the SHR by CaMKII and c-FOS expression. Therefore, the hypothesized segmental defect in the anterior forebrain of the SHR produces network consequences leading to behavioral alteration in t he attentional activity and emotional domains, Subchronic treatment with me tilphenidate (MP) that. is known to block the reuptake of biogenic amines ( mainly DA) produced network remodeling which are known to be paralleled by behavioral modifications in the attentive activity and emotional domains. I mperspective, the results from this model system that features the main asp ects of attention-deficit hyperactivity disorder (ADHD), can be useful for the understanding of the neural substrates of hyperactivity and attention d eficits and possibly for an early diagnosis and appropriate treatment of AD HD children. (C) 2000 Elsevier Science Ltd. All rights reserved.