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

• Published in: European neuropsychopharmacology Vol. 18; no. 2; p. 147
• Main Authors: Deutsch, Stephen I, Rosse, Richard B, Schwartz, Barbara L, Schooler, Nina R, Gaskins, Brooke L, Long, Katrice D, Mastropaolo, John
• Format: Journal Article
• Language: English
• Published: Netherlands 01.02.2008
• Subjects: Analysis of Variance; Animals; Behavior, Animal - drug effects; Cholinesterase Inhibitors - therapeutic use; Cytidine Diphosphate Choline - therapeutic use; Disease Models, Animal; Dizocilpine Maleate - pharmacology; Drug Interactions; Drug Therapy, Combination; Excitatory Amino Acid Antagonists - pharmacology; Galantamine - therapeutic use; Male; Mice; Nootropic Agents - therapeutic use; Schizophrenia - drug therapy
• ISSN: 0924-977X

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.