title: Effects of CDP-choline and the combination of CDP-choline and galantamine differ in an animal model of schizophrenia: development of a selective alpha7 nicotinic acetylcholine receptor agonist strategy.
abstract: The regionally selective reduction of expression of the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) in schizophrenia underlies impaired sensory inhibition, a possible endophenotype of the disorder. This ligand-gated ion channel receptor has been proposed as a pharmacotherapeutic target in schizophrenia. The current study examined the effect of CDP-choline alone and the combination of CDP-choline and galantamine, administered acutely and once-daily for five consecutive days, in an animal model of NMDA receptor hypofunction that is relevant to schizophrenia. The results support the allosteric modulatory influence of galantamine on CDP-choline; however, individual doses of CDP-choline and galantamine must be carefully titrated in order to achieve optimal levels of alpha7 nAChR "agonism" that may be necessary for the desired therapeutic effect.
authors.affiliation: Mental Health Service Line (116A), Department of Veterans Affairs Medical Center, 50 Irving Street, NW, Washington, DC 20422, United States. Stephen.Deutsch@med.va.gov
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Deutsch
authors.forename: Richard B
authors.initials: RB
authors.lastname: Rosse
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Schwartz
authors.forename: Nina R
authors.initials: NR
authors.lastname: Schooler
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Gaskins
authors.forename: Katrice D
authors.initials: KD
authors.lastname: Long
authors.forename: John
authors.initials: J
authors.lastname: Mastropaolo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003566:Cytidine Diphosphate Choline / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005702:Galantamine / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018697:Nootropic Agents / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D005702:Galantamine; D003566:Cytidine Diphosphate Choline; D016291:Dizocilpine Maleate