Reduced transduction mechanisms in the anterior accumbal interface of an animal model of Attention-Deficit Hyperactivity Disorder.
The aim of this study was to map the neural substrates of attention-deficit hyperactivity disorder (ADHD) in the spontaneously hypertensive rat (SHR), which is thought to be a model for ADHD. To this aim, the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and transcription factors (TF) were used as markers. The focus of interest was the nucleus accumbens complex (ACB) which is thought to be an interface between limbic and motor systems. Juvenile, male rats of the SHR line and Wistar-Kyoto (WKY) controls were perfused and the brains processed for immunocytochemistry 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 the ACB; (ii) SHR had a reduced number of CaMKII-positive elements in anterior 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 the core of the ACB in the SHR. In contrast, there was an increased basal 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 accumbal complex of SHR, associated to the higher number of binding sites 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 the key to the understanding of ADHD.
Institute of Human Anatomy, Second University of Naples, Italy.
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M
Papa
J A
JA
Sergeant
A G
AG
Sadile
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis; D008297:Male; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000473:pathology; D009714:Nucleus Accumbens / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity; D014157:Transcription Factors / Q000032:analysis
D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases