title: Nicotinic receptors and lurasidone-mediated reversal of phencyclidine-induced deficit in novel object recognition.
abstract: BACKGROUND
  Enhancement of cholinergic function via nicotinic acetylcholine (ACh) receptor (nAChR) agonism is a potential approach for the treatment of cognitive impairment associated with schizophrenia (CIAS). Some atypical antipsychotic drugs (AAPDs) enhance ACh release in rodent brain, indirectly stimulating these receptors. Here, we elucidate which nAChR subtypes mediate novel object recognition (NOR) in normal rats and contribute to the ability of the AAPD, lurasidone, to improve the NOR deficit in sub-chronic (sc) phencyclidine (PCP)-treated rats, a model for CIAS.
  
  
  METHODS
  The ability of lurasidone and nAChR ligands to reverse the scPCP-induced deficit in NOR was assessed in female, Long-Evans rats.
  
  
  RESULTS
  The broad acting nAChR antagonist, mecamylamine (MEC), induced a NOR deficit in normal rats. The NOR deficit secondary to scPCP was reversed by either selective α4β2* nAChR agonism (A-85380) or α7 nAChRs agonism (PNU-282987); these effects were blocked by DHβE and MLA, selective antagonists of α4β2* and α7 nAChR, respectively. The ability of lurasidone to reverse the scPCP-induced NOR deficit was blocked by MEC, but not MLA or DHβE. However, sub-effective doses (SED) of either A-85380 or PNU-282987 potentiated the ability of SED lurasidone to reverse the scPCP-induced NOR deficit.
  
  
  CONCLUSIONS
  These results identify both α4β2* and α7 nAChRs as candidates for enhancing the ability of lurasidone and other AAPDs, which increase the release of ACh, to improve CIAS.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, 303 East Chicago Ave #7-101, Chicago, IL 60611, USA; Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. Electronic address: masanori-miyauchi@ds-pharma.co.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyauchi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, 303 East Chicago Ave #7-101, Chicago, IL 60611, USA. Electronic address: nichole.neugebauer@northwestern.edu.
authors.forename: Nichole M
authors.initials: NM
authors.lastname: Neugebauer
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, 303 East Chicago Ave #7-101, Chicago, IL 60611, USA; Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. Electronic address: yoshihiro-oyamada@ds-pharma.co.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oyamada
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, 303 East Chicago Ave #7-101, Chicago, IL 60611, USA. Electronic address: h-meltzer@northwestern.edu.
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
mesh_terms: D000818:Animals; D001384:Azetidines / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000069056:Lurasidone Hydrochloride / Q000494:pharmacology*; D008464:Mecamylamine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D010622:Phencyclidine; D011897:Random Allocation; D020318:Rats, Long-Evans; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: C104288:A 85380; D001384:Azetidines; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D018697:Nootropic Agents; C498513:PNU-282987; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D008464:Mecamylamine; D010622:Phencyclidine; D000069056:Lurasidone Hydrochloride
keywords: Acetylcholine; Atypical antipsychotic drug; Nicotinic acetylcholine receptors; Novel object recognition; Phencyclidine