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Effects of chronic treatment with L‐alpha‐glycerylphosphorylcholine on hippocampal cholinergic transmission in the rat

Effects of chronic treatment with L‐alpha‐glycerylphosphorylcholine on hippocampal cholinergic... L‐alpha‐glycerylphosphorylcholine (alpha‐GPC) has been proposed for the treatment of age‐related cognitive disturbances. In the rat the compound prevents the learning impair‐ ment and the retrograde amnesia both induced by scopolamine and this effect appears to be correlated with an increase of hippocampal acetylcholine production and release. Since drugs ameliorating learning and memory are usually administered for long periods of time, here we investigated the effects of chronic treatment with alpha‐GPC on the neurochemical parameters linked to hippocampal cholinergic transmission. The data show that an in‐ creased (3H)acetylcholine (ACh) release was detectable in rats chronically exposed to alpha‐GPC and killed 3 hr after the last administration, suggesting that tolerance did not develop in these experimental conditions. An alpha‐GPC‐induced selective desensitization of hippocampal muscarinic M‐2 receptor function was also found. This event was charac‐ terized by a decreased responsiveness of adenylate cyclase to carbachol inhibition in the absence of changes in M‐2 receptor density. This effect could be relevant in view of M‐2 receptor presynaptic location and function in inhibiting ACh release. In contrast with M‐2 receptor, M‐1 receptor density and function were not significantly changed by the treatment. The present data suggest that alpha‐GPC could be proposed as a useful drug for the chronic treatment of memory deficit. © 1992 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Development Research Wiley

Effects of chronic treatment with L‐alpha‐glycerylphosphorylcholine on hippocampal cholinergic transmission in the rat

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References (32)

Publisher
Wiley
Copyright
Copyright © 1992 Wiley‐Liss, Inc., A Wiley Company
ISSN
0272-4391
eISSN
1098-2299
DOI
10.1002/ddr.430270307
Publisher site
See Article on Publisher Site

Abstract

L‐alpha‐glycerylphosphorylcholine (alpha‐GPC) has been proposed for the treatment of age‐related cognitive disturbances. In the rat the compound prevents the learning impair‐ ment and the retrograde amnesia both induced by scopolamine and this effect appears to be correlated with an increase of hippocampal acetylcholine production and release. Since drugs ameliorating learning and memory are usually administered for long periods of time, here we investigated the effects of chronic treatment with alpha‐GPC on the neurochemical parameters linked to hippocampal cholinergic transmission. The data show that an in‐ creased (3H)acetylcholine (ACh) release was detectable in rats chronically exposed to alpha‐GPC and killed 3 hr after the last administration, suggesting that tolerance did not develop in these experimental conditions. An alpha‐GPC‐induced selective desensitization of hippocampal muscarinic M‐2 receptor function was also found. This event was charac‐ terized by a decreased responsiveness of adenylate cyclase to carbachol inhibition in the absence of changes in M‐2 receptor density. This effect could be relevant in view of M‐2 receptor presynaptic location and function in inhibiting ACh release. In contrast with M‐2 receptor, M‐1 receptor density and function were not significantly changed by the treatment. The present data suggest that alpha‐GPC could be proposed as a useful drug for the chronic treatment of memory deficit. © 1992 Wiley‐Liss, Inc.

Journal

Drug Development ResearchWiley

Published: Jan 1, 1992

Keywords: memory; acetylcholine release; muscarinic receptors; choline precursors

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