Multiple evidence of a segmental defect in the anterior forebrain of an animal model of hyperactivity and attention deficit.
Molecular biology and microscope imaging techniques were used to map putative neural substrates of hyperactivity and attention deficit in an animal model, the juvenile prehypertensive male spontaneously hypertensive rat (SHR). We have studied in anterior forebrain sections of SHR and Wistar-Kyoto Normotensive (WKY) controls the spatial distribution of neural markers such as: (i) dopamine (DA) D-1 and D-2 receptor families by radioligand binding studies; (ii) the Ca2+/calmodulin-dependent protein kinase II (CaMKII); and (iii) the transcription regulators of gene expression (TFs) c-FOS and JUN-B by Immunocytochemistry (ICC). Microcomputer-assisted high-resolution image analysis showed in the SHR a higher density of DA D-1 receptors and a lower density of D-3 autoreceptors paralleled by a reduced number of elements positive for CaMKII and TFs in a restricted segment of the anterior forebrain that included the most rostral portions of the caudate-putamen, pole and shell of the nucleus accumbens and olfactory tubercle. The differential rostro-caudal distribution of D-1 receptors and D-3 autoreceptors is discussed in the light of current hypotheses of DA mesocorticolimbic system functioning. In addition, the segmental defect was partially reversed by subchronic treatment with a DA re-uptake blocker, Methylphenidate (MPH; 3 mg/kg) and by environmental stimulation during the fifth and sixth postnatal week. The findings are consistent with the role of genetic determinants and environmental factors in the phenotypic expression of hyperactivity and attention deficit.
Sadile
A G
AG
Department of Human Physiology F. Bottazzi, Second University of Naples (SUN), Italy. adolfo.sadile@unina2.it
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology*; D001345:Autoradiography; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis; D003627:Data Interpretation, Statistical; D016762:Genes, fos / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D010477:Perfusion; D016548:Prosencephalon / Q000473:pathology*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects
D016755:Proto-Oncogene Proteins c-jun; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases