title: α7 nicotinic ACh receptor-deficient mice exhibit sustained attention impairments that are reversed by β2 nicotinic ACh receptor activation.
abstract: OBJECTIVE
  Disruptions of executive function, including attentional deficits, are a hallmark of a number of diseases. ACh in the prefrontal cortex regulates attentive behaviour; however, the role of α7 nicotinic ACh receptor (α7nAChR) in attention is contentious.
  
  
  METHODS
  In order to probe attention, we trained both wild-type and α7nAChR knockout mice on a touch screen-based five-choice serial reaction time task (5-CSRT). Following training procedures, we then tested sustained attention using a probe trial experiment. To further differentiate the role of specific nicotinic receptors in attention, we then tested the effects of both α7nAChR and β2nAChR agonists on the performance of both wild-type and knockout mice on the 5-CSRT task.
  
  
  RESULTS
  At low doses, α7nAChR agonists improved attentional performance of wild-type mice, while high doses had deleterious effects on attention. α7nAChR knockout mice displayed deficits in sustained attention that were not ameliorated by α7nAChR agonists. However, these deficits were completely reversed by the administration of a β2nAChR agonist. Furthermore, administration of a β2nAChR agonist in α7nAChR knockout mice elicited similar biochemical response in the prefrontal cortex as the administration of α7nAChR agonists in wild-type mice.
  
  
  CONCLUSIONS
  Our experiments reveal an intricate relationship between distinct nicotinic receptors to regulate attentional performance and provide the basis for targeting β2nAChRs pharmacologically to decrease attentional deficits due to a dysfunction in α7nAChRs.
authors.affiliation: Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.|Graduate Program in Neuroscience, University of Western Ontario, London, ON, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kolisnyk
authors.affiliation: Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.|Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Al-Onaizi
authors.affiliation: Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.|Graduate Program in Neuroscience, University of Western Ontario, London, ON, Canada.|Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.|Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada.
authors.forename: Vania F
authors.initials: VF
authors.lastname: Prado
authors.affiliation: Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.|Graduate Program in Neuroscience, University of Western Ontario, London, ON, Canada.|Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.|Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada.
authors.forename: Marco A M
authors.initials: MA
authors.lastname: Prado
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D018345:Mice, Knockout; D018722:Nicotinic Agonists / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000172:deficiency / Q000502:physiology*
chemical_list: D007555:Isoxazoles; D018722:Nicotinic Agonists; D011759:Pyrrolidines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C088383:3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole