title: Aberrant glutamate signaling in the prefrontal cortex and striatum of the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  Attention-deficit/hyperactivity disorder (ADHD) is thought to involve hypofunctional catecholamine systems in the striatum, nucleus accumbens, and prefrontal cortex (PFC); however, recent clinical evidence has implicated glutamate dysfunction in the pathophysiology of ADHD. Recent studies show that increased stimulation of dopamine D2 and D4 receptors causes inhibition of N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, respectively. The spontaneously hypertensive rat (SHR) model of ADHD combined type (C) has been found to have a hypofunctional dopamine system in the ventral striatum, nucleus accumbens, and PFC compared to the control Wistar Kyoto (WKY) strain.
  
  
  OBJECTIVE
  Based on the current understanding of typical dopamine-glutamate interactions, we hypothesized that the SHR model of ADHD would have a hyperfunctional glutamate system terminating in the striatum, nucleus accumbens, and PFC.
  
  
  RESULTS
  High-speed amperometric recordings combined with four-channel microelectrode arrays to directly measure glutamate dynamics showed increased evoked glutamate release in the PFC (cingulate and infralimbic cortices, p < 0.05) and also in the striatum (p < 0.05) of the SHR (ADHD-C) as compared to the WKY. Finally, glutamate uptake was discovered to be aberrant in the PFC, but not the striatum, of the SHR when compared to the control WKY strain.
  
  
  CONCLUSIONS
  These results suggest that the glutamatergic system in the PFC of the SHR model of ADHD is hyperfunctional and that targeting glutamate in the PFC could lead to the development of novel therapeutics for the treatment of ADHD.
authors.affiliation: Department of Anatomy and Neurobiology, University of Kentucky Chandler Medical Center, Lexington, KY, 40536, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Miller
authors.forename: Francois
authors.initials: F
authors.lastname: Pomerleau
authors.forename: Peter
authors.initials: P
authors.lastname: Huettl
authors.forename: Greg A
authors.initials: GA
authors.lastname: Gerhardt
authors.forename: Paul E A
authors.initials: PE
authors.lastname: Glaser
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D002491:Central Nervous System Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008839:Microelectrodes; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D011189:Potassium Chloride / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D002491:Central Nervous System Agents; D018698:Glutamic Acid; D011189:Potassium Chloride