Region-specific elevation of D₁ receptor-mediated neurotransmission in the nucleus accumbens of SHR, a rat model of attention deficit/hyperactivity disorder

Neuropharmacology. 2012 Sep;63(4):547-54. doi: 10.1016/j.neuropharm.2012.04.031. Epub 2012 May 10.


Spontaneously hypertensive rats (SHR) are widely used as a rat model of attention deficit/hyperactivity disorder (AD/HD). Here, we conducted neurochemical and behavioral studies in SHR to clarify the topographical alterations in neurotransmissions linked to their behavioral abnormalities. In the open-field test, juvenile SHR showed a significant hyperactivity in ambulation and rearing as compared with Wistar Kyoto rats (WKY). Brain mapping analysis of Fos-immunoreactivity (IR) revealed that SHR showed a marked increase in Fos expression in the core part (AcC) of the nucleus accumbens (NAc). Small to moderate increases were also observed in the shell part of the NAc and some regions of the cerebral cortex (e.g., parietal association cortex). These changes in Fos expression were region-specific and the Fos-IR levels in other brain regions (e.g., hippocampus, amygdala, striatum, thalamus and hypothalamus) were unaltered. In addition, treatment of SHR with the selective D₁ antagonist SCH-23390 significantly reversed both behavioral hyperactivity and elevated Fos expression in the AcC and cerebral cortex. The present study suggests that D₁ receptor-mediated neurotransmission in the AcC is region-specifically elevated in SHR, which could be responsible for behavioral hyperactivity.

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Attention Deficit Disorder with Hyperactivity / metabolism*
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Behavior, Animal / drug effects
  • Benzazepines / therapeutic use
  • Brain Mapping
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Dopamine Antagonists / therapeutic use
  • Exploratory Behavior / drug effects
  • Male
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / pathology
  • Organ Specificity
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Inbred SHR
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism*
  • Synaptic Transmission* / drug effects
  • Up-Regulation* / drug effects


  • Benzazepines
  • Dopamine Antagonists
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-fos
  • Receptors, Dopamine D1
  • SCH 23390