Effect of subchronic galantamine treatment on neuronal nicotinic and muscarinic receptor subtypes in transgenic mice overexpressing human acetylcholinesterase

Neuropharmacology
Marie M SvedbergAgneta Nordberg

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 change...Continue Reading

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Citations

Feb 8, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Seok-Joo ParkHyoung-Chun Kim
May 12, 2009·Behavioural Brain Research·Steven AnzaloneLisa Savage
Nov 5, 2019·Frontiers in Molecular Neuroscience·Azadeh KaramiTaher Darreh-Shori
Oct 11, 2005·The Journal of Pharmacology and Experimental Therapeutics·C M HernandezA V Terry
Dec 16, 2005·The Journal of Pharmacology and Experimental Therapeutics·Christina UngerAgneta Nordberg
Oct 19, 2010·Analytical Chemistry·Maria Rowena N MontonJohn D Brennan

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