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.
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.
Deutsch
Stephen I
SI
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
Rosse
Richard B
RB
Schwartz
Barbara L
BL
Schooler
Nina R
NR
Gaskins
Brooke L
BL
Long
Katrice D
KD
Mastropaolo
John
J
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*
D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D005702:Galantamine; D003566:Cytidine Diphosphate Choline; D016291:Dizocilpine Maleate