title: Psychostimulants and atomoxetine alter the electrophysiological activity of prefrontal cortex neurons, interaction with catecholamine and glutamate NMDA receptors.
abstract: BACKGROUND
  Attention-deficit hyperactivity disorder (ADHD) is the most frequently diagnosed neuropsychiatric disorder in childhood. Currently available ADHD drugs include the psychostimulants methylphenidate (MPH) and D-amphetamine (D-AMP), acting on norepinephrine and dopamine transporters/release, and atomoxetine (ATX), a selective norepinephrine uptake inhibitor. Recent evidence suggests an involvement of glutamate neurotransmission in the pathology and treatment of ADHD, via mechanisms to be clarified.
  
  
  OBJECTIVE
  We have investigated how ADHD drugs could modulate, through interaction with catecholamine receptors, basal and glutamate-induced excitability of pyramidal neurons in the prefrontal cortex (PFC), a region which plays a major role in control of attention and impulsivity.
  
  
  METHODS
  We have used the technique of extracellular single-unit recording in anaesthetised rats coupled with microiontophoresis.
  
  
  RESULTS
  Both MPH (1-3 mg/kg) and D-AMP (1-9 mg/kg) increased the firing activity of PFC neurons in a dopamine D1 receptor-dependent manner. ATX administration (1-6 mg/kg) also increased the firing of neurons, but this effect is not significantly reversed by D1 (SCH 23390) or alpha1 (prazosin) receptor antagonists but potentiated by alpha2 antagonist (yohimbine). All drugs induced a clear potentiation of the excitatory response of PFC neurons to the microiontophoretic application of the glutamate agonist N-methyl-D-aspartate (NMDA), but not to the glutamate agonist α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). The potentiating effect of D-AMP on NMDA-induced activation of PFC neurons was partially reversed or prevented by dopamine D1 receptor blockade.
  
  
  CONCLUSIONS
  Our data shows that increase in excitability of PFC neurons in basal conditions and via NMDA receptor activation may be involved in the therapeutic response to ADHD drugs.
authors.affiliation: Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Di Miceli
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gronier
mesh_terms: D000818:Animals; D000069445:Atomoxetine Hydrochloride / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D017983:Receptors, Catecholamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D018091:Receptors, AMPA; D017983:Receptors, Catecholamine; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride