title: Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.
abstract: BACKGROUND
  Nicotine and nicotinic agonists have been shown to improve attentional function. Nicotinic receptors are easily desensitized, and all nicotinic agonists are also desensitizing agents. Although both receptor activation and desensitization are components of the mechanism that mediates the overall effects of nicotinic agonists, it is not clear how each of the two opposed actions contributes to attentional improvements. Sazetidine-A has high binding affinity at α4β2 nicotinic receptors and causes a relatively brief activation followed by a long-lasting desensitization of the receptors. Acute administration of sazetidine-A has been shown to significantly improve attention by reversing impairments caused by the muscarinic cholinergic antagonist scopolamine and the NMDA glutamate antagonist dizocilpine.
  
  
  METHODS
  In the current study, we tested the effects of chronic subcutaneous infusion of sazetidine-A (0, 2, or 6 mg/kg/day) on attention in Sprague-Dawley rats. Furthermore, we investigated the effects of chronic sazetidine-A treatment on attentional impairment induced by an acute administration of 0.02 mg/kg scopolamine.
  
  
  RESULTS
  During the first week period, the 6-mg/kg/day sazetidine-A dose significantly reversed the attentional impairment induced by scopolamine. During weeks 3 and 4, the scopolamine-induced impairment was no longer seen, but sazetidine-A (6 mg/kg/day) significantly improved attentional performance on its own. Chronic sazetidine-A also reduced response latency and response omissions.
  
  
  CONCLUSIONS
  This study demonstrated that similar to its acute effects, chronic infusions of sazetidine-A improve attentional performance. The results indicate that the desensitization of α4β2 nicotinic receptors with some activation of these receptors may play an important role in improving effects of sazetidine-A on attention.
authors.affiliation: Department of Psychiatry, 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: Yingxian
authors.initials: Y
authors.lastname: Xiao
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*; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D055104:Infusions, Subcutaneous; D008024:Ligands; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011485:Protein Binding; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D001384:Azetidines; D008024:Ligands; D018727:Muscarinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C514816:sazetidine-A; D012601:Scopolamine