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Chronic treatment with an acetylcholine synthesis precursor, alpha‐glycerylphosphorylcholine, alters brain parameters linked to cholinergic transmission and passive avoidance behavior
Author(s) -
Govoni Stefano,
Lopez Clara M.,
Battaini Fiorenzo,
Trabucchi Marco
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430260407
Subject(s) - acetylcholine , amnesia , hippocampus , cholinergic , pharmacology , chemistry , cerebral cortex , cortex (anatomy) , endocrinology , medicine , psychology , neuroscience , psychiatry
The present study extends previous observations on the acuta treatment with alpha‐glycerylphosphorylcholine (GPC), a putative acetylcholine (ACh) precursor, and investigates the effect of chronic treatment with this drug on scopolamine‐induced amnesia and on ACh release in the rat. The drug acutely administered antagonizes the amnesic effect of scopolamine (0.75 mg/kg s.c.) in passive avoidance experiments. The effect peaked at 600 mg/kg i.g. and lasted up to 30 hr. Potassium‐stimulated release of ACh from slices of hippocampus and cerebral cortex was measured after various doses of GPC. The dose curve study indicated that GPC was able to increase ACh release in the hippocampus already at the dose of 75 mg/kg i.g. The maximum effect was obtained with 300 mg/kg i.g. (147% of the control values). The increase of the ACh release reached a maximum 3 hrfollowing the administration, then declined toward control values. In the cortex, the effect was much less pronounced and shorter than in the hippocampus. The repeated (100 and 300 mg/kg i.g.; 22 days) GPC administration effectively antagonized scopolamine‐induced amnesia, indicating that there was no tolerance to this effect of GPC. While both doses were behaviorally active only 300 mg/kg was able to increase ACh release from hippocampus ( + 271 %) and cortex ( + 57%). The data support the hypothesis that GPC improves behavioral performance in passive avoidance through an action on cholinergic transmission. On the other hand, it should be stressed that the action on ACh release is observed in a narrow time window in contrast to the long lasting effect on behavior. It is tempting to speculate that the effect on ACh may be related to cortical activation and important but not sufficient to explain the antagonism of scopolamine‐induced amnesia. Along this line other mechanisms, possibly triggered by the action on ACh, may contribute to mediate the behavioral effect of GPC. © 1992 Wiley‐Liss, Inc.