title: Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats.
abstract: BACKGROUND
  Neuronal nicotinic receptor systems have been shown to play key roles in cognition. Nicotine and nicotinic analogs improve attention and nicotinic antagonists impair it. This study was conducted to investigate the role of α4β2 nicotinic receptors in sustained attention using a novel selective α4β2 nicotinic receptor ligand, sazetidine-A.
  
  
  METHODS
  Female rats were trained to perform the signal detection task to a stable baseline of accuracy. The rats were injected with saline, sazetidine-A (0.01, 0.03, and 0.1 mg/kg), dizocilpine (0.05 mg/kg), or their combination; or, in another experiment, the rats were injected with the same doses of sazetidine-A, scopolamine (0.02 mg/kg), or their combination.
  
  
  RESULTS
  Percent hit and percent correct rejection showed that dizocilpine caused significant (p < 0.025) impairments in performance, which were significantly reversed by each of the sazetidine-A doses. Response omissions were significantly (p < 0.05) increased by dizocilpine, and this was also significantly reversed by each of the sazetidine-A doses. None of the sazetidine-A doses had significant effects on hit, correct rejection, or response omissions when given alone. Scopolamine also caused significant (p < 0.0005) impairments in percent hit and percent correct rejection and increased response omissions, which were significantly attenuated by all the sazetidine-A doses for percent hit and response omissions and by the highest dose of sazetidine-A for percent correct rejection. Both scopolamine and dizocilpine significantly (p < 0.0005) increased response latency, an effect which was significantly attenuated by sazetidine-A coadministration.
  
  
  CONCLUSIONS
  These studies imply an important role for α4β2 nicotinic receptors in improving sustained attention under conditions that disrupt it. Very low doses of sazetidine-A or drugs with a similar profile may provide therapeutic benefit for reversing attentional impairment in patients suffering from mental disorders and/or cognitive impairment.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 104790, Durham, NC 27710, USA. Azadi@duke.edu
authors.forename: Amir H
authors.initials: AH
authors.lastname: Rezvani
authors.forename: Marty
authors.initials: M
authors.lastname: Cauley
authors.forename: Hannah
authors.initials: H
authors.lastname: Sexton
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Xiao
authors.forename: Milton L
authors.initials: ML
authors.lastname: Brown
authors.forename: Mikell A
authors.initials: MA
authors.lastname: Paige
authors.forename: Brian E
authors.initials: BE
authors.lastname: McDowell
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Kellar
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects*; D001384:Azetidines / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008024:Ligands; D015394:Molecular Structure; D010775:Photic Stimulation; D011597:Psychomotor Performance / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology*
chemical_list: D001384:Azetidines; D008024:Ligands; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C514816:sazetidine-A; D016291:Dizocilpine Maleate; D012601:Scopolamine