title: Chronic nicotine improves short-term memory selectively in a G72 mouse model of schizophrenia.
abstract: OBJECTIVE
  The prevalence of smoking in schizophrenia patients is exceptionally high; it is not known why but many researchers suggest that smoking constitutes a form of self-medication. Among the symptoms of schizophrenia that may be improved by nicotine are cognitive deficits. Hence, we studied the effects of long-term nicotine administration on cognition in a genetic animal model of schizophrenia susceptibility, G72-transgenic (G72Tg) mice.
  
  
  METHODS
  The effect of long-term nicotine or saline, administered by osmotic minipumps, on different cognitive domains was assessed in G72Tg mice and controls using a battery of behavioural tests. To investigate the mechanism underlying phenotypic differences, quantitative autoradiographic mapping of nACh receptor subtypes was performed in forebrain structures to explore effects of chronic nicotine exposure on nACh receptor density in wild-type (WT) and G72Tg mice.
  
  
  RESULTS
  Genotype significantly affected the cognitive effects of chronic nicotine administration. Whereas chronic nicotine disrupted cognitive performance in WT mice, it was effective at restoring impaired prepulse inhibition, working memory and social recognition in G72Tg mice. However, long-term spatial learning was further impaired by nicotine in transgenic animals. In contrast, associative learning was protected by G72-expression against the adverse nicotine effects seen in WT animals. G72-expression did not decisively influence nicotine-induced up-regulation of the α4β2*subtype, whereas α7nACh receptor density was differentially altered by genotype or by a genotype·treatment interaction in specific brain areas, most notably hippocampal subregions.
  
  
  CONCLUSIONS
  Our data support the hypothesis that nicotine self-medication of schizophrenics improves cognitive symptoms, possibly by facilitating nicotine-induced α7nACh receptor activation in the hippocampus.
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hambsch
authors.forename: H
authors.initials: H
authors.lastname: Keyworth
authors.forename: J
authors.initials: J
authors.lastname: Lind
authors.forename: D M
authors.initials: DM
authors.lastname: Otte
authors.forename: I
authors.initials: I
authors.lastname: Racz
authors.forename: I
authors.initials: I
authors.lastname: Kitchen
authors.forename: A
authors.initials: A
authors.lastname: Bailey
authors.forename: A
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D018697:Nootropic Agents / Q000008:administration & dosage*; D010641:Phenotype; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D012565:Schizophrenic Psychology; D012919:Social Behavior; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C579166:Chrna7 protein, mouse; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018722:Nicotinic Agonists; D018697:Nootropic Agents; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine
keywords: G72 mouse model; G72/G30 gene locus; chronic nicotine; cognition; nicotinic acetylcholine receptor; receptor autoradiography; schizophrenia; self-medication; short-term memory; susceptibility gene