title: Impaired attention is central to the cognitive deficits observed in alpha 7 deficient mice.
abstract: alpha7-Nicotinic acetylcholine receptors (alpha7-nAChR) have been implicated in a range of cognitive deficits in schizophrenia. Therefore we examined alpha7-nAChR knockout (KO), heterozygote (HT) and wildtype (WT) littermate mice in the 5-CSR (a rodent model of sustained attention) and odour span (a novel mouse working memory paradigm) tasks, and related performance to nAChR density. Whilst there was no difference between groups in baseline 5-CSR task performance, alpha7-nAChR KO's exhibited significantly higher omission levels compared to WT mice on increasing the attentional load, with HT mice performing at an intermediate level. Furthermore, alpha7-nAChR KO mice were significantly impaired in the odour span task when compared to WT mice, in a pattern consistent with impaired attention. These behavioural deficits were associated with the loss of alpha7-nAChRs, as alpha4beta2-nAChR density was unaltered in these mice. Thus these studies intimate that the attentional impairment in alpha7-nAChR transgenic mice maybe core to other deficits in cognition.
authors.affiliation: Astellas CNS Research in Edinburgh, The University of Edinburgh, The Chancellor's Building, 49 Little France Crescent, EH16 4SB, UK.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Young
authors.forename: Nicola
authors.initials: N
authors.lastname: Crawford
authors.forename: John S
authors.initials: JS
authors.lastname: Kelly
authors.forename: Lorraine E
authors.initials: LE
authors.lastname: Kerr
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Marston
authors.forename: Christopher
authors.initials: C
authors.lastname: Spratt
authors.forename: Keith
authors.initials: K
authors.lastname: Finlayson
authors.forename: John
authors.initials: J
authors.lastname: Sharkey
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000470:Alkaloids / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology* / Q000235:genetics; D001392:Azocines / Q000493:pharmacokinetics; D001522:Behavior, Animal; D002755:Choice Behavior / Q000502:physiology; D003072:Cognition Disorders / Q000150:complications* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D051379:Mice; D018345:Mice, Knockout; D018733:Nicotinic Antagonists / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D011807:Quinolizines / Q000493:pharmacokinetics; D011930:Reaction Time / Q000235:genetics; D011978:Receptors, Nicotinic / Q000172:deficiency* / Q000502:physiology; D014316:Tritium / Q000493:pharmacokinetics; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000093843:Quinolizidine Alkaloids
chemical_list: D000157:Aconitine; D000470:Alkaloids; D001392:Azocines; D018733:Nicotinic Antagonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; D014316:Tritium; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse; C054634:methyllycaconitine; C004712:cytisine; D000093843:Quinolizidine Alkaloids