title: α₂- and β-adrenoceptors involvement in nortriptyline modulation of auditory sustained attention and impulsivity.
abstract: BACKGROUND
  The catecholamine innervation of the prefrontal cortex controls attentional focus and inhibits inappropriate behavioral responses. The mechanism of action with which norepinephrine (NE) reuptake inhibitors modulate these cognitive functions has not been fully investigated.
  
  
  OBJECTIVE
  We investigated the effect of systemic administration of the NE reuptake blocker nortriptyline (NT) on attention and impulsivity using an auditory sustained attention task. The task was designed to assess impulsive behavior and the maintenance of attentional focus to an auditory stimulus presented at interresponse time durations (IRT) between 5 and 80 s.
  
  
  RESULTS
  NT (2.0 but not 3.0 mg/kg) improved sustained attention and decreased the percentage of premature responses without changing their latency. To better understand the adrenergic component of NT action, we tested the effect of noradrenergic receptor antagonists alone or together with NT. The α(2)-receptor antagonist yohimbine, the α(1)-receptor antagonist prazosin, or the β-receptor antagonist propranolol alone did not significantly affect attentive performance or premature responses. However, the beneficial effects of NT on sustained attention and premature responses were attenuated by pretreatment with either yohimbine or propranolol. On the contrary, prazosin did not affect the NT-mediated improvement in sustained attention.
  
  
  CONCLUSIONS
  We conclude that sustained attention displays an inverse U-shaped dependence on NT, mediated-at least in part-by α(2)- and β-adrenoceptors. We speculate that low doses of NT improve performance by maximizing the phasic release of NE, while higher doses of NT would elevate tonic levels of NE, thus producing suboptimal levels of phasically released NE.
authors.affiliation: Laboratory of Synaptic and Cellular Physiology, School of Behavioral and Brain Sciences, University of Texas at Dallas/GR41, 800 West Campbell Road, Richardson, TX 75080, USA.
authors.forename: Swagata
authors.initials: S
authors.lastname: Roychowdhury
authors.forename: Zulma
authors.initials: Z
authors.lastname: Peña-Contreras
authors.forename: Jason
authors.initials: J
authors.lastname: Tam
authors.forename: Amulya
authors.initials: A
authors.lastname: Yadlapalli
authors.forename: Lu
authors.initials: L
authors.lastname: Dinh
authors.forename: Justin Andrew
authors.initials: JA
authors.lastname: Nichols
authors.forename: Debarshi
authors.initials: D
authors.lastname: Basu
authors.forename: Marco
authors.initials: M
authors.lastname: Atzori
mesh_terms: D000161:Acoustic Stimulation; D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007175:Impulsive Behavior; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D009661:Nortriptyline / Q000008:administration & dosage / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D011433:Propranolol; D009661:Nortriptyline; D009638:Norepinephrine; D011224:Prazosin