RGD Reference Report - The usefulness of the spontaneously hypertensive rat to model attention-deficit/hyperactivity disorder (ADHD) may be explained by the differential expression of dopamine-related genes in the brain. - Rat Genome Database

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The usefulness of the spontaneously hypertensive rat to model attention-deficit/hyperactivity disorder (ADHD) may be explained by the differential expression of dopamine-related genes in the brain.

Authors: Li, Q  Lu, G  Antonio, GE  Mak, YT  Rudd, JA  Fan, M  Yew, DT 
Citation: Li Q, etal., Neurochem Int. 2007 May;50(6):848-57. Epub 2007 Mar 1.
RGD ID: 2311591
Pubmed: PMID:17395336   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuint.2007.02.005   (Journal Full-text)

Spontaneously hypertensive rats (SHR) are considered to represent a genetic animal model for attention-deficit hyperactivity disorder (ADHD). In the present studies, we compared the locomotor activity, learning and memory functions of juvenile male SHR, with age- and gender-matched genetic control Wistar-Kyoto rats (WKY). In addition, we investigated potential differences in brain morphology by magnetic resonance imaging (MRI). In other complimentary studies of the central nervous system, we used real-time PCR to examine the levels of several dopaminergic-related genes, including those coding for the five major subtypes of dopamine receptor (D1, D2, D3, D4 and D5), those coding for enzymes responsible for synthesizing tyrosine hydroxylase and dopamine-beta-hydroxylase, and those coding for the dopamine transporter. Our data revealed that SHR were more active than WKY in the open field (OF) test. Also, SHR appeared less attentive, exhibiting inhibition deficit, but in the absence of memory deficits relative to spatial learning. The MRI studies revealed that SHR had a significantly smaller vermis cerebelli and caudate-putamen (CPu), and there was also a significantly lower level of dopamine D4 receptor gene expression and protein synthesis in the prefrontal cortex (PFC) of SHR. However, there were no significant differences between the expression of other dopaminergic-related genes in the midbrain, prefrontal cortex, temporal cortex, striatum, or amygdala of SHR and WKY. The data are similar to the situation seen in ADHD patients, relative to normal volunteers, and it is possible that the hypo-dopaminergic state involves a down regulation of dopamine D4 receptors, rather than a general down-regulation of catecholamine synthesis. In conclusion, the molecular and behavioural data that we obtained provide new information that may be relevant to understanding ADHD in man.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
attention deficit hyperactivity disorder  ISODrd4 (Rattus norvegicus)2311591; 2311591mRNA and protein:decreased expression:frontal association cortexRGD 
attention deficit hyperactivity disorder  IEP 2311591mRNA and protein:decreased expression:frontal association cortexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Drd4  (dopamine receptor D4)

Genes (Mus musculus)
Drd4  (dopamine receptor D4)

Genes (Homo sapiens)
DRD4  (dopamine receptor D4)

Objects referenced in this article
Gene DRD1 dopamine receptor D1 Homo sapiens
Gene DRD2 dopamine receptor D2 Homo sapiens
Gene DRD3 dopamine receptor D3 Homo sapiens
Gene DRD5 dopamine receptor D5 Homo sapiens
Gene Drd1 dopamine receptor D1 Mus musculus
Gene Drd2 dopamine receptor D2 Mus musculus
Gene Drd3 dopamine receptor D3 Mus musculus
Gene Drd5 dopamine receptor D5 Mus musculus
Gene Drd1 dopamine receptor D1 Rattus norvegicus
Gene Drd2 dopamine receptor D2 Rattus norvegicus
Gene Drd3 dopamine receptor D3 Rattus norvegicus
Gene Drd5 dopamine receptor D5 Rattus norvegicus

Additional Information