REDUCED TRANSDUCTION MECHANISMS IN THE ANTERIOR ACCUMBAL INTERFACE OFAN ANIMAL-MODEL OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER

The aim of this study was to map the neural substrates of attention-de ficit hyperactivity disorder (ADHD) in the spontaneously hypertensive rat (SHR), which is thought to be a model for ADHD. To this aim, the C a2+/calmodulin-dependent protein kinase II (CaMKII) and transcription factors (TF) were used as markers. The focus of interest was the nucle us accumbens complex (ACB) which is thought to be an interface between limbic and motor systems. Juvenile, male rats of the SHR line and Wis tar-Kyoto (WKY) controls were perfused and the brains processed for im munocytochemistry for CaMKII and the TF peptides of the FOS, JUN-B and ZIF-268 families. The results revealed that: (i) in both groups there were more CaMKII-positive neurones in the shell than in the core of t he ACB; (ii) SHR had a reduced number of CaMKII-positive elements in a nterior portions of the shell; and (iii) SHR had a lower expression of peptide products of the FOS family (c-FOS, in particular) and ZIF-268 . In addition, there was a lower expression of c-FOS and zif-268 in th e core of the ACB in the SHR. In contrast: there was an increased basa l level of JUN-B in the core of the ACB of SHR. The reduced number of CaMKII and TF-positive elements in the most rostral portions of the ac cumbal complex of SHR, associated to the higher number of binding site s for the DA D-1/D-5 subtype, appears as a discrete alteration in the prosomeric development of the anterior basal forebrain and could be th e key to the understanding of ADHD. (C) 1998 Elsevier Science B.V. All rights reserved.