title: Effect of subchronic galantamine treatment on neuronal nicotinic and muscarinic receptor subtypes in transgenic mice overexpressing human acetylcholinesterase.
abstract: Overexpression of acetylcholinesterase (AChE) in mice causes cholinergic deficits with memory impairment. In this study, AChE overexpressing (hAChE-Tg) and control (FVB/N) mice were treated with the AChE inhibitor (AChEI) galantamine (4 mg/kg/day) for 10 days. The concentration of galantamine in plasma was 75-80 ng/ml. The inhibition of AChE was 20% in red blood cells (RBC) and 30% in brain cortical tissue. A significant increase in [(3)H]cytisine (alpha4 nicotinic receptor) binding was measured in the CA1 and CA3 area of the hippocampus of FVB/N mice following galantamine treatment. Similarly, a significant increase in [(125)I]alphabungarotoxin (alpha7 nicotinic receptor) binding was found in the frontal cortex, retrosplenial gr. cortex, motor cortex and thalamus in galantamine treated FVB/N compared to saline treated mice. No significant changes in nicotinic receptor binding sites were observed in galantamine treated hAChE-Tg mice. Significant decreases in the muscarinic receptors measured by [(3)H]AF-DX-384 (M2 muscarinic receptor) and [(3)H]pirenzepine (M1 muscarinic receptor) were observed in several brain regions of galantamine treated FVB/N and hAChE-Tg mice. This study shows regional and receptor subtype specific changes in the nicotinic receptor subtypes compared to the muscarinic receptors following galantamine treatment in FVB/N and hAChE-Tg mice.
authors.affiliation: Division of Molecular Neuropharmacology, Department of Neurotec, Karolinska Institutet, Huddinge University Hospital B84, S-141 86 Stockholm, Sweden.
authors.forename: Marie M
authors.initials: MM
authors.lastname: Svedberg
authors.forename: Ivan
authors.initials: I
authors.lastname: Bednar
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
mesh_terms: D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005260:Female; D005702:Galantamine / Q000008:administration & dosage*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000096:biosynthesis; D011976:Receptors, Muscarinic / Q000096:biosynthesis*; D011978:Receptors, Nicotinic / Q000096:biosynthesis*
chemical_list: D002800:Cholinesterase Inhibitors; D021122:Protein Subunits; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D005702:Galantamine; D000110:Acetylcholinesterase