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

  • Alzheimer's Disease and Related Disorders - Original Article
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Abstract

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 α7 and non-α7 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 [3H]-EPI to measure non-α7 nAChRs and [3H]-MLA to measure α7 nAChRs. In the cortex, all compounds tested at the higher doses significantly increased the levels of both [3H]-EPI and [3H]-MLA. In the hippocampus all compounds significantly increased [3H]-EPI but had no effect on [3H]-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-α7 or α7 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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Abbreviations

AD:

Alzheimer’s disease

ChEI:

Acetylcholinesterase inhibitor

nAChR:

Nicotinic acetylcholine receptor

EPI:

Epibatidine

MLA:

Methyllyconitine

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Acknowledgments

This work was funded by an unrestricted grant from Eisai Inc. and Pfizer Inc., the Erik and Ese Banck Clinical Research Center, NIA P30 AG 019610 and the Sun Health Research Institute.

Disclosures: Dr Reid has nothing to disclose. Dr Sabbagh is on the speaker’s bureau for Pfizer, Eisai, Forest and Novartis. He is a consultant for Lilly and Eisai. Dr Sabbagh receives clinical research funding from Eisai, Pfizer, GSK, Novartis, Avid, Wyeth, Lilly, Medivation, Abbott and Elan.

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  1. Erik and Ese Banck Clinical Research Center, 8716 Production Avenue, San Diego, CA, 92121, USA

    Richard T. Reid

  2. The Cleo Roberts Center for Clinical Research, Sun Health Research Institute, 10515 W. Santa Fe Dr, Sun City, AZ, 85351, USA

    Marwan N. Sabbagh

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Correspondence to Richard T. Reid.

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Reid, R.T., Sabbagh, M.N. Effects of cholinesterase inhibitors on rat nicotinic receptor levels in vivo and in vitro. J Neural Transm 115, 1437–1444 (2008). https://doi.org/10.1007/s00702-008-0107-7

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  • DOI: https://doi.org/10.1007/s00702-008-0107-7

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