Effects of cholinesterase inhibitors on rat nicotinic receptor levels in vivo and in vitro.

Effects of cholinesterase inhibitors on rat nicotinic receptor levels in vivo and in vitro. Research Abstract Details 

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Effects of cholinesterase inhibitors on rat nicotinic receptor levels in vivo and in vitro. Abstract Text:

Cholinesterase inhibitors (ChEIs) are the mainstay of treatment for AD but differ by secondary mechanisms of action. We determine the effects of sub-chronic dosing of ChEIs on alpha7 and non-alpha7 nAChRs and determine if differences can be observed between them. Sprague-Dawley rats were administered donepezil, galantamine; rivastigmine at two doses each, in saline SQ twice daily or with nicotine (0.4 mg/kg) as a positive control. After 14 days the animals were sacrificed, and the levels of nAChRs were measured using [(3)H]-EPI to measure non-alpha7 nAChRs and [(3)H]-MLA to measure alpha7 nAChRs. In the cortex, all compounds tested at the higher doses significantly increased the levels of both [(3)H]-EPI and [(3)H]-MLA. In the hippocampus all compounds significantly increased [(3)H]-EPI but had no effect on [(3)H]-MLA binding. No effects were observed in the striatum with treatment. There were no differences observed among the ChEIs. In cell cultures, none of the ChEIs increased non-alpha7 or alpha7 receptor binding. Treatment with ChEIs result in similar increases in receptor levels which suggest that the increases in nAChRs may be due simply to the increases in synaptic levels of acetylcholine.

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Effects of cholinesterase inhibitors on rat nicotinic receptor levels in vivo and in vitro. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of neural transmission (Vienna, Austria :

VOLUME: 115

Page Numbers: 1437-44

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ISSN: 0300-9564

DAY: 26

MONTH: 08

YEAR: 2008

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LANGUAGE: eng

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AFFILIATION: Erik and Ese Banck Clinical Research Center, 8716 Production Avenue, San Diego, CA, 92121, USA, richard.reid@thebanckcenter.org.

Country: Austria

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MEDLINETA: J Neural Transm

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